136 results on '"Jan Polak"'
Search Results
2. Hypoxia-Induced Sarcoplasmic Reticulum Ca2+ Leak Is Reversed by Ryanodine Receptor Stabilizer JTV-519 in HL-1 Cardiomyocytes
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Minh Duc Trinh, Ivana Fišerová, Lukáš Vacek, Marek Heide, Jan Pala, Petr Tousek, and Jan Polak
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calcium ,heart failure ,obstructive sleep apnea ,hypoxia ,ryanodine receptor ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background: To assess whether hypoxia, as can be found in obstructive sleep apnea syndrome, is causally associated with the development of heart failure through a direct effect on calcium leakage from the sarcoplasmic reticulum. Methods: The impact of hypoxia on sarcoplasmic reticulum calcium leakage and expression of RyR2 (ryanodine receptor2) and SERC2a (sarcoplasmic reticulum Ca2+ATPase 2a) was investigated together with the outcomes of JTV-519 and S107 treatment. HL-1 cardiomyocytes were cultured for 7 days on gas-permeable cultureware under control (12% O2) or hypoxic (1% O2) conditions with or without JTV-519 or S107. SRCL was assessed using a Fluo-5N probe. Gene and protein expression was analyzed using qPCR and western blotting. Results: Hypoxic exposure increased sarcoplasmic reticulum calcium leakage by 39% and reduced RyR2 gene expression by 52%. No effect on RyR2 protein expression was observed. Treatment with 1µM JTV-519 reduced sarcoplasmic reticulum calcium leakage by 52% and 35% under control and hypoxic conditions, respectively. Administration of 1 µM JTV-519 increased RyR2 gene expression by 89% in control conditions. No effect on SRCL, RyR2, or SERC2a gene, or protein expression was observed with S107 treatment. Conclusion: Hypoxia increased sarcoplasmic reticulum calcium leakage which was ameliorated by JTV-519 treatment independently of gene or protein expression. JTV-519 rep-resents a possible treatment for obstructive sleep apnea-associated HF.
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- 2022
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3. Isoprenaline modified the lipidomic profile and reduced β-oxidation in HL-1 cardiomyocytes: In vitro model of takotsubo syndrome
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Ivana Fiserova, Minh Duc Trinh, Moustafa Elkalaf, Lukas Vacek, Marek Heide, Stanislava Martinkova, Kamila Bechynska, Vit Kosek, Jana Hajslova, Ondrej Fiser, Petr Tousek, and Jan Polak
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takotsubo ,isoprenaline ,cardiomyocyte ,lipid ,fatty acid ,mitochondria ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Recent studies have suggested a pathogenetic link between impaired mitochondria and Takotsubo syndrome (TTS), which is closely connected with catecholamine overstimulation, poor outcomes, and changes in lipid metabolism. We investigated the changes in lipid metabolism at the level of fatty acid β-oxidation and changes in the intracellular lipidomic spectrum. The immortalized cell line of HL-1 cardiomyocytes was used in this study as an established in vitro model of TTS. The cells were exposed to the non-selective β-agonist isoprenaline (ISO) for acute (2 h) and prolonged (24 h) periods. We investigated the impact on mitochondrial adenosine 5’-triphosphate (ATP) production and β-oxidation using real-time cell metabolic analysis, total lipid content, and changes in the lipidomic spectrum using high-performance liquid chromatography (HPLC) and mass spectrometry. Furthermore, modifications of selected lipid transporters were determined using real-time – polymerase chain reaction (RT-PCR) and/or Western blot techniques. By choosing this wide range of targets, we provide a detailed overview of molecular changes in lipid metabolism during catecholamine overstimulation. The present study demonstrates that acute exposure to ISO decreased ATP production by up to 42.2%, and prolonged exposure to ISO decreased β-oxidation by 86.4%. Prolonged exposure to ISO also increased lipid accumulation by 4%. Lipid spectrum analysis of prolonged exposure to ISO showed a reduced concentration of cardioprotective and an increased concentration of lipotoxic lipid molecules during long-term exposure. Decreased lipid utilization can lead to higher intracellular lipid accumulation and the formation of lipotoxic molecules. Changes in the lipid spectrum can induce pathophysiological signaling pathways leading to cardiomyocyte remodeling or apoptosis. Thus, changes in lipid metabolism induced by excessive doses of catecholamines may cause TTS and contribute to a progression of heart failure, which is at increased risk after a TTS episode.
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- 2022
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4. From Structural Optimization Results to Parametric CAD Modeling—Automated, Skeletonization-Based Truss Recognition
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Jan Polak and Michał Nowak
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feature recognition ,biomimetic structural optimization ,mechanical design ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
This paper presents an automated, skeletonization-based feature recognition system designed for use with biomimetic structural optimization results. It enables importing optimization results back to the CAD system as a set of parameterized geometries. The system decomposes the output of the structural optimization system into a set of simple CAD features, cylinders and spheres, enabling continuation of mechanical design workflow using native CAD representation. The system was designed to work in a fully automated mode accepting 3D objects as an input. The system uses mesh skeletonization to generate an initial solution which is refined using an evolutionary algorithm for the 3D geometry reconstruction. The system is designed as the last step of structural optimization. Applied for industrial use, it preserves unique features of this approach, such as excluding parts of the domain from optimization. The biomimetic topology optimization was used for structural optimization for all presented examples. The proposed algorithm is demonstrated using two cases: well-recognized cantilever beam optimization and industrial application of the structural optimization. For both cases, resultant geometry stress distribution is provided and analyzed.
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- 2023
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5. Obstructive sleep apnoea increases lipolysis and deteriorates glucose homeostasis in patients with type 2 diabetes mellitus
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Minh Duc Trinh, Andrea Plihalova, Jan Gojda, Katerina Westlake, Jan Spicka, Zuzana Lattova, Martin Pretl, and Jan Polak
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Medicine ,Science - Abstract
Abstract Obstructive sleep apnoea (OSA) is associated with type 2 diabetes mellitus (T2DM). However, mechanisms mediating association between these two conditions remain unclear. This study investigated, whether the OSA-associated changes in adipose tissue lipolysis might contribute to impaired glucose homeostasis in patient with T2DM. Thirty-five matched subjects were recruited into three groups: T2DM + severe OSA (T2DM + OSA, n = 11), T2DM with mild/no OSA (T2DM, n = 10) and healthy controls (n = 14). Subcutaneous abdominal adipose tissue microdialysis assessed spontaneous, epinephrine- and isoprenaline-stimulated lipolysis. Glucose metabolism was assessed by intravenous glucose tolerance test. Spontaneous lipolysis was higher in the T2DM + OSA compared with the T2DM (60.34 ± 23.40 vs. 42.53 ± 10.16 μmol/L, p = 0.013), as well as epinephrine-stimulated lipolysis (236.84 ± 103.90 vs. 167.39 ± 52.17 µmol/L, p
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- 2021
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6. Muscle Lipid Oxidation Is Not Affected by Obstructive Sleep Apnea in Diabetes and Healthy Subjects
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Zuzana Lattova, Lucie Slovakova, Andrea Plihalova, Jan Gojda, Moustafa Elkalaf, Katerina Westlake, and Jan Polak
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obstructive sleep apnea ,type 2 diabetes mellitus ,free fatty acids ,lipid utilization ,IVGTT ,glucose intolerance ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The molecular mechanisms linking obstructive sleep apnea (OSA) with type 2 diabetes mellitus (T2DM) remain unclear. This study investigated the effect of OSA on skeletal muscle lipid oxidation in nondiabetic controls and in type 2 diabetes (T2DM) patients. Forty-four participants matched for age and adiposity were enrolled: nondiabetic controls (control, n = 14), nondiabetic patients with severe OSA (OSA, n = 9), T2DM patients with no OSA (T2DM, n = 10), and T2DM patients with severe OSA (T2DM + OSA, n = 11). A skeletal muscle biopsy was performed; gene and protein expressions were determined and lipid oxidation was analyzed. An intravenous glucose tolerance test was performed to investigate glucose homeostasis. No differences in lipid oxidation (178.2 ± 57.1, 161.7 ± 22.4, 169.3 ± 50.9, and 140.0 ± 24.1 pmol/min/mg for control, OSA, T2DM, and T2DM+OSA, respectively; p > 0.05) or gene and protein expressions were observed between the groups. The disposition index, acute insulin response to glucose, insulin resistance, plasma insulin, glucose, and HBA1C progressively worsened in the following order: control, OSA, T2DM, and T2DM + OSA (p for trend
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- 2023
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7. Hypoxia Induces Saturated Fatty Acids Accumulation and Reduces Unsaturated Fatty Acids Independently of Reverse Tricarboxylic Acid Cycle in L6 Myotubes
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Lukas Vacek, Ales Dvorak, Kamila Bechynska, Vit Kosek, Moustafa Elkalaf, Minh Duc Trinh, Ivana Fiserova, Katerina Pospisilova, Lucie Slovakova, Libor Vitek, Jana Hajslova, and Jan Polak
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hypoxia ,reverse TCA ,L6 myotubes ,glutamin ,lipids ,obstructive sleep apnea ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Obstructive sleep apnea syndrome, characterized by repetitive episodes of tissue hypoxia, is associated with several metabolic impairments. Role of fatty acids and lipids attracts attention in its pathogenesis for their metabolic effects. Parallelly, hypoxia-induced activation of reverse tricarboxylic acid cycle (rTCA) with reductive glutamine metabolism provides precursor molecules for de novo lipogenesis. Gas-permeable cultureware was used to culture L6-myotubes in chronic hypoxia (12%, 4% and 1% O2) with 13C labelled glutamine and inhibitors of glutamine uptake or rTCA-mediated lipogenesis. We investigated changes in lipidomic profile, 13C appearance in rTCA-related metabolites, gene and protein expression of rTCA-related proteins and glutamine transporters, glucose uptake and lactate production. Lipid content increased by 308% at 1% O2, predominantly composed of saturated fatty acids, while triacylglyceroles containing unsaturated fatty acids and membrane lipids (phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositol) decreased by 20-70%. rTCA labelling of malate, citrate and 2-hydroxyglutarate increased by 4.7-fold, 2.2-fold and 1.9-fold in 1% O2, respectively. ATP-dependent citrate lyase inhibition in 1% O2 decreased lipid amount by 23% and increased intensity of triacylglyceroles containing unsaturated fatty acids by 56-80%. Lactate production increased with hypoxia. Glucose uptake dropped by 75% with progression of hypoxia from 4% to 1% O2. Protein expression remained unchanged. Altogether, hypoxia modified cell metabolism leading to lipid composition alteration and rTCA activation.
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- 2022
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8. Interaction of Diet/Lifestyle Intervention and TCF7L2 Genotype on Glycemic Control and Adiposity among Overweight or Obese Adults: Big Data from Seven Randomized Controlled Trials Worldwide
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Tao Huang, Zhenhuang Zhuang, Yoriko Heianza, Dianjianyi Sun, Wenjie Ma, Wenxiu Wang, Meng Gao, Zhe Fang, Emilio Ros, Liana C. Del Gobbo, Jordi Salas-Salvadó, Miguel A. Martínez-González, Jan Polak, Markku Laakso, Arne Astrup, Dominique Langin, Jorg Hager, Gabby Hul, Torben Hansen, Oluf Pedersen, Jean-Michel Oppert, Wim H. M. Saris, Peter Arner, Montserrat Cofán, Sujatha Rajaram, Jaakko Tuomilehto, Jaana Lindström, Vanessa D. de Mello, Alena Stancacova, Matti Uusitupa, Mathilde Svendstrup, Thorkild I. A. Sørensen, Christopher D. Gardner, Joan Sabaté, Dolores Corella, J. Alfredo Martinez, and Lu Qi
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Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
Objective. The strongest locus which associated with type 2 diabetes (T2D) by the common variant rs7903146 is the transcription factor 7-like 2 gene (TCF7L2). We aimed to quantify the interaction of diet/lifestyle interventions and the genetic effect of TCF7L2 rs7903146 on glycemic traits, body weight, or waist circumference in overweight or obese adults in several randomized controlled trials (RCTs). Methods. From October 2016 to May 2018, a large collaborative analysis was performed by pooling individual-participant data from 7 RCTs. These RCTs reported changes in glycemic control and adiposity of the variant rs7903146 after dietary/lifestyle-related interventions in overweight or obese adults. Gene treatment interaction models which used the genetic effect encoded by the allele dose and common covariates were applicable to individual participant data in all studies. Results. In the joint analysis, a total of 7 eligible RCTs were included (n=4,114). Importantly, we observed a significant effect modification of diet/lifestyle-related interventions on the TCF7L2 variant rs7903146 and changes in fasting glucose. Compared with the control group, diet/lifestyle interventions were related to lower fasting glucose by -3.06 (95% CI, -5.77 to -0.36) mg/dL (test for heterogeneity and overall effect: I2=45.1%, p
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- 2021
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9. Technical Feasibility and Physiological Relevance of Hypoxic Cell Culture Models
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Jiri Pavlacky and Jan Polak
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hypoxia ,cell culture ,animal model ,in vitro model ,pericellular oxygen ,oxygen concentration ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Hypoxia is characterized as insufficient oxygen delivery to tissues and cells in the body and is prevalent in many human physiology processes and diseases. Thus, it is an attractive state to experimentally study to understand its inner mechanisms as well as to develop and test therapies against pathological conditions related to hypoxia. Animal models in vivo fail to recapitulate some of the key hallmarks of human physiology, which leads to human cell cultures; however, they are prone to bias, namely when pericellular oxygen concentration (partial pressure) does not respect oxygen dynamics in vivo. A search of the current literature on the topic revealed this was the case for many original studies pertaining to experimental models of hypoxia in vitro. Therefore, in this review, we present evidence mandating for the close control of oxygen levels in cell culture models of hypoxia. First, we discuss the basic physical laws required for understanding the oxygen dynamics in vitro, most notably the limited diffusion through a liquid medium that hampers the oxygenation of cells in conventional cultures. We then summarize up-to-date knowledge of techniques that help standardize the culture environment in a replicable fashion by increasing oxygen delivery to the cells and measuring pericellular levels. We also discuss how these tools may be applied to model both constant and intermittent hypoxia in a physiologically relevant manner, considering known values of partial pressure of tissue normoxia and hypoxia in vivo, compared to conventional cultures incubated at rigid oxygen pressure. Attention is given to the potential influence of three-dimensional tissue cultures and hypercapnia management on these models. Finally, we discuss the implications of these concepts for cell cultures, which try to emulate tissue normoxia, and conclude that the maintenance of precise oxygen levels is important in any cell culture setting.
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- 2020
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10. The Clinical Impact of Systematic Screening for Obstructive Sleep Apnea in a Type 2 Diabetes Population—Adherence to the Screening-Diagnostic Process and the Acceptance and Adherence to the CPAP Therapy Compared to Regular Sleep Clinic Patients
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Katerina Westlake, Veronika Dostalova, Andrea Plihalova, Martin Pretl, and Jan Polak
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sleep apnea ,diabetes ,screening ,CPAP acceptance ,CPAP adherence ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Obstructive sleep apnea (OSA) is a common disorder in Type 2 diabetes (T2D) patients further increasing their already high cardiovascular risk. As T2D patients typically not report OSA symptoms, systematic screening for OSA in this population is warranted. We aimed to determine the readiness of T2D patients to undergo screening and to compare their adherence to continuous positive airway pressure (CPAP) therapy with “regular” sleep clinic patients who typically seek medical advice on their own initiative. We therefore recruited 494 consecutive T2D patients and offered them OSA screening using home sleep monitoring (type IV device). All participants in high risk of moderate-to-severe OSA were recommended home sleep apnea testing (HSAT) followed by CPAP therapy. Patients were followed-up for 12 months and outcomes compared to 228 consecutive sleep clinic patients undergoing HSAT. Among 307 screened T2D patients, 94 (31%) were identified at high risk of moderate-to-severe OSA. Subsequently, 54 patients underwent HSAT, 51 were recommended, and 38 patients initiated CPAP (acceptance 75%). Among 228 sleep clinic patients, 92 (40%) were recommended and 74 patients initiated CPAP (acceptance 80%). After 1 year, 15 (39%) T2D and 29 (39%) sleep clinic patients showed good CPAP adherence (use ≥ 4 h/night ≥ 70% nights). In conclusion, 20 T2D patients needed to be screened in order to obtain one successfully treated patient. OSA screening in T2D patients identified 31% with moderate-to-severe OSA. Once diagnosed, their CPAP acceptance and adherence did not differ from sleep clinic patients. However, the reasons for the high dropout during the screening-diagnostic process impacting the overall success of the screening program need to be identified and addressed.
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- 2018
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11. The Effect of Hypoxia and Metformin on Fatty Acid Uptake, Storage, and Oxidation in L6 Differentiated Myotubes
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Martina Musutova, Moustafa Elkalaf, Natalie Klubickova, Michal Koc, Stanislav Povysil, Jan Rambousek, Beatriz Volckaert, Frantisek Duska, Minh Duc Trinh, Martin Kalous, Jan Trnka, Kamila Balusikova, Jan Kovar, and Jan Polak
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hypoxia ,myotubes ,free fatty acids ,FFA oxidation ,FFA uptake ,metformin ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Metabolic impairments associated with obstructive sleep apnea syndrome (OSA) are linked to tissue hypoxia, however, the explanatory molecular and endocrine mechanisms remain unknown. Using gas-permeable cultureware, we studied the chronic effects of mild and severe hypoxia on free fatty acid (FFA) uptake, storage, and oxidation in L6 myotubes under 20, 4, or 1% O2. Additionally, the impact of metformin and the peroxisome proliferator-activated receptor (PPAR) β/δ agonist, called GW501516, were investigated. Exposure to mild and severe hypoxia reduced FFA uptake by 37 and 32%, respectively, while metformin treatment increased FFA uptake by 39% under mild hypoxia. GW501516 reduced FFA uptake under all conditions. Protein expressions of CD36 (cluster of differentiation 36) and SCL27A4 (solute carrier family 27 fatty acid transporter, member 4) were reduced by 17 and 23% under severe hypoxia. Gene expression of UCP2 (uncoupling protein 2) was reduced by severe hypoxia by 81%. Metformin increased CD36 protein levels by 28% under control conditions and SCL27A4 levels by 56% under mild hypoxia. Intracellular lipids were reduced by mild hypoxia by 18%, while in controls only, metformin administration further reduced intracellular lipids (20% O2) by 36%. Finally, palmitate oxidation was reduced by severe hypoxia, while metformin treatment reduced non-mitochondrial O2 consumption, palmitate oxidation, and proton leak at all O2 levels. Hypoxia directly reduced FFA uptake and intracellular lipids uptake in myotubes, at least partially, due to the reduction in CD36 transporters. Metformin, but not GW501516, can increase FFA uptake and SCL27A4 expression under mild hypoxia. Described effects might contribute to elevated plasma FFA levels and metabolic derangements in OSA.
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- 2018
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12. Blockade of Endothelin-1 Receptor Type B Ameliorates Glucose Intolerance and Insulin Resistance in a Mouse Model of Obstructive Sleep Apnea
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Jan Polak, Naresh M. Punjabi, and Larissa A. Shimoda
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obstructive sleep apnea ,endothelin ,endothelin receptor ,bosentan ,diabetes ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Obstructive sleep apnea (OSA) is associated with insulin resistance (IR) and glucose intolerance. Elevated endothelin-1 (ET-1) levels have been observed in OSA patients and in mice exposed to intermittent hypoxia (IH). We examined whether pharmacological blockade of type A and type B ET-1 receptors (ETA and ETB) would ameliorate glucose intolerance and IR in mice exposed to IH. Subcutaneously implanted pumps delivered BQ-123 (ETA antagonist; 200 nmol/kg/day), BQ-788 (ETB antagonist; 200 nmol/kg/day) or vehicle (saline or propyleneglycol [PG]) for 14 days in C57BL6/J mice (10/group). During treatment, mice were exposed to IH (decreasing the FiO2 from 20.9% to 6%, 60/h) or intermittent air (IA). After IH or IA exposure, insulin (0.5 IU/kg) or glucose (1 mg/kg) was injected intraperitoneally and plasma glucose determined after injection and area under glucose curve (AUC) was calculated. Fourteen-day IH increased fasting glucose levels (122 ± 7 vs. 157 ± 8 mg/dL, PG: 118 ± 6 vs. 139 ± 8; both p
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- 2018
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13. Response to: Letter to the Editor concerning the Article 'Adolescent Idiopathic Scoliosis: A 71 Cases Study Ascertaining that Straightening Is Possible, and a New Etiological Hypothesis'
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Jan Polak
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Medicine - Published
- 2015
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14. Change in Proportional Protein Intake in a 10-Week Energy-Restricted Low- or High-Fat Diet, in Relation to Changes in Body Size and Metabolic Factors
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Tanja Stocks, Moira A. Taylor, Lars Ängquist, Ian A. MacDonald, Peter Arner, Claus Holst, Jean-Michel Oppert, J.Alfredo Martinez, Stephan Rössner, Jan Polak, Dominique Langin, Wim H.M. Saris, Arne Astrup, and Thorkild I.A. Sørensen
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Obesity ,Dietary fats ,Dietary proteins ,Lipids ,Blood glucose ,Nutrition. Foods and food supply ,TX341-641 ,Nutritional diseases. Deficiency diseases ,RC620-627 - Abstract
Objective: To investigate in a secondary analysis of a randomised trial the effects of a low-/high-fat diet and reported change from baseline in energy% from protein (prot%), in relation to changes in body size and metabolic factors. Methods: Obese adults (n = 771) were randomised to a 600 kcal energy-deficient low-fat (20-25 fat%) or high-fat (40-45 fat%) diet over 10 weeks. Dietary intake data at baseline and during the intervention were available in 585 completers. We used linear regression to calculate the combined effects of randomised group and groups of prot% change (2) on outcomes. Results: The low-fat group with >2 prot% increase lost 1.1 kg more weight (p = 0.03) and reduced cholesterol by 0.25 mmol/l more (p = 0.003) than the high-fat group with >2 prot% decrease. These differences were 2.5-fold and 1.8-fold greater than the differences between the low-fat and high-fat groups while not considering prot% change. The high-fat group reduced plasma triglycerides more than the low-fat group, but not compared to those in the low-fat group with >2 units prot% increase (p fat-protein interaction = 0.01). Conclusions: Under energy restriction, participants on a low-fat diet who had increased the percentage energy intake from protein showed the greatest reduction in weight and cholesterol, and a triglyceride reduction equally large to that of participants on a high-fat diet.
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- 2013
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15. The Effect of Pericellular Oxygen Levels on Proteomic Profile and Lipogenesis in 3T3-L1 Differentiated Preadipocytes Cultured on Gas-Permeable Cultureware.
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Martin Weiszenstein, Nela Pavlikova, Moustafa Elkalaf, Petr Halada, Ondrej Seda, Jan Trnka, Jan Kovar, and Jan Polak
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Medicine ,Science - Abstract
Pericellular oxygen concentration represents an important factor in the regulation of cell functions, including cell differentiation, growth and mitochondrial energy metabolism. Hypoxia in adipose tissue has been associated with altered adipokine secretion profile and suggested as a possible factor in the development of type 2 diabetes. In vitro experiments provide an indispensable tool in metabolic research, however, physical laws of gas diffusion make prolonged exposure of adherent cells to desired pericellular O2 concentrations questionable. The aim of this study was to investigate the direct effect of various O2 levels (1%, 4% and 20% O2) on the proteomic profile and triglyceride accumulation in 3T3-L1 differentiated preadipocytes using gas-permeable cultureware. Following differentiation of cells under desired pericellular O2 concentrations, cell lysates were subjected to two-dimensional gel electrophoresis and protein visualization using Coomassie blue staining. Spots showing differential expression under hypoxia were analyzed using matrix-assisted laser desorption/ionization mass spectrometry. All identified proteins were subjected to pathway analysis. We observed that protein expression of 26 spots was reproducibly affected by 4% and 1% O2 (17 upregulated and 9 downregulated). Pathway analysis showed that mitochondrial energy metabolism and triglyceride synthesis were significantly upregulated by hypoxia. In conclusion, this study demonstrated the direct effects of pericellular O2 levels on adipocyte energy metabolism and triglyceride synthesis, probably mediated through the reversed tricarboxylic acid cycle flux.
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- 2016
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16. Acute exposure to long-chain fatty acids impairs α2-adrenergic receptor-mediated antilipolysis in human adipose tissue
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Jan Polak, Cédric Moro, David Bessière, Jindra Hejnova, Marie A. Marquès, Magda Bajzova, Max Lafontan, Francois Crampes, Michel Berlan, and Vladimir Stich
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lipolysis ,catecholamines ,high-fat meal ,exercise ,microdialysis ,lipid mobilization ,Biochemistry ,QD415-436 - Abstract
The acute in vitro and in vivo effects of long-chain fatty acids (LCFAs) on the regulation of adrenergic lipolysis were investigated in human adipose tissue. The effect of a 2 h incubation, without or with LCFA (200 μmol/l), on basal and hormonally induced lipolysis was tested in vitro on isolated fat cells. The lipolytic response to epinephrine was enhanced by suppression of the antilipolytic α2-adrenergic effect. Then, healthy lean and obese male subjects performed a 45 min exercise bout at 50% of their heart rate reserve either after an overnight fast or 3 h after a high-fat meal (HFM: 95% fat, 5% carbohydrates). Subcutaneous adipose tissue lipolysis was measured by microdialysis in the presence or absence of an α-antagonist (phentolamine). In vivo, a HFM increased plasma levels of nonesterified fatty acids in lean and obese subjects. In both groups, the HFM did not alter hormonal responses to exercise. Under fasting conditions, the α2-adrenergic antilipolytic effect was more pronounced in obese than in lean subjects. The HFM totally suppressed the α2-adrenergic antilipolytic effect in lean and obese subjects during exercise. LCFAs per se, in vitro as well as in vivo, suppress α2-adrenergic-mediated antilipolysis in adipose tissue. LCFA-mediated suppression of antilipolytic pathways represents another mechanism whereby a high fat content in the diet might increase adipose tissue lipolysis.
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- 2007
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17. The Impact of Full-Length, Trimeric and Globular Adiponectin on Lipolysis in Subcutaneous and Visceral Adipocytes of Obese and Non-Obese Women.
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Zuzana Wedellova, Zuzana Kovacova, Michaela Tencerova, Tomas Vedral, Lenka Rossmeislova, Michaela Siklova-Vitkova, Vladimir Stich, and Jan Polak
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Medicine ,Science - Abstract
Contribution of individual adiponectin isoforms to lipolysis regulation remains unknown. We investigated the impact of full-length, trimeric and globular adiponectin isoforms on spontaneous lipolysis in subcutaneous abdominal (SCAAT) and visceral adipose tissues (VAT) of obese and non-obese subjects. Furthermore, we explored the role of AMPK (5'-AMP-activated protein kinase) in adiponectin-dependent lipolysis regulation and expression of adiponectin receptors type 1 and 2 (AdipoR1 and AdipoR2) in SCAAT and VAT. Primary adipocytes isolated from SCAAT and VAT of obese and non-obese women were incubated with 20 µg/ml of: A) full-length adiponectin (physiological mixture of all adiponectin isoforms), B) trimeric adiponectin isoform or C) globular adiponectin isoform. Glycerol released into media was used as a marker of lipolysis. While full-length adiponectin inhibited lipolysis by 22% in non-obese SCAAT, globular isoform inhibited lipolysis by 27% in obese SCAAT. No effect of either isoform was detected in non-obese VAT, however trimeric isoform inhibited lipolysis by 21% in obese VAT (all p
- Published
- 2013
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18. TFAP2B influences the effect of dietary fat on weight loss under energy restriction.
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Tanja Stocks, Lars Angquist, Karina Banasik, Marie N Harder, Moira A Taylor, Jörg Hager, Peter Arner, Jean-Michel Oppert, J Alfredo Martinez, Jan Polak, Francis Rousseau, Dominique Langin, Stephan Rössner, Claus Holst, Ian A MacDonald, Yoichiro Kamatani, Andreas F H Pfeiffer, Marie Kunesova, Wim H M Saris, Torben Hansen, Oluf Pedersen, Arne Astrup, and Thorkild I A Sørensen
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Medicine ,Science - Abstract
BackgroundNumerous gene loci are related to single measures of body weight and shape. We investigated if 55 SNPs previously associated with BMI or waist measures, modify the effects of fat intake on weight loss and waist reduction under energy restriction.Methods and findingsRandomized controlled trial of 771 obese adults. (RegistrationISRCTN25867281.) One SNP was selected for replication in another weight loss intervention study of 934 obese adults. The original trial was a 10-week 600 kcal/d energy-deficient diet with energy percentage from fat (fat%) in range of 20-25 or 40-45. The replication study used an 8-weeks diet of 880 kcal/d and 20 fat%; change in fat% intake was used for estimation of interaction effects. The main outcomes were intervention weight loss and waist reduction. In the trial, mean change in fat% intake was -12/+4 in the low/high-fat groups. In the replication study, it was -23/-12 among those reducing fat% more/less than the median. TFAP2B-rs987237 genotype AA was associated with 1.0 kg (95% CI, 0.4; 1.6) greater weight loss on the low-fat, and GG genotype with 2.6 kg (1.1; 4.1) greater weight loss on the high-fat (interaction p-value; p = 0.00007). The replication study showed a similar (non-significant) interaction pattern. Waist reduction results generally were similar. Study-strengths include (i) the discovery study randomised trial design combined with the replication opportunity (ii) the strict dietary intake control in both studies (iii) the large sample sizes of both studies. Limitations are (i) the low minor allele frequency of the TFAP2B polymorphism, making it hard to investigate non-additive genetic effects (ii) the different interventions preventing identical replication-discovery study designs (iii) some missing data for non-completers and dietary intake. No adverse effects/outcomes or side-effects were observed.ConclusionsUnder energy restriction, TFAP2B may modify the effect of dietary fat intake on weight loss and waist reduction.
- Published
- 2012
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19. Long-term hypoxia exposure impairs metabolic pathways of de novo lipogenesis in young mouse adipocytes
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Lucie Slovakova, Katerina Pospisilova, Jiri Vavra, and Jan Polak
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Physiology - Abstract
Introduction: Obstructive sleep apnea syndrome, manifested by tissue hypoxia, is causally linked with the development of metabolic diseases such as Type 2 diabetes. Although there is convincing epidemiological evidence, molecular mechanisms mediating the adverse metabolic effects remain unclear. Hypoxia may play an important role and modulate metabolic pathways in young adipocytes including the utilization of glucose and acetate or the activation of the reverse tricarboxylic acid cycle (rTCA) leading to increase de novo lipogenesis and excessive fat accumulation. The aim of this study was to investigate the impact of long-term hypoxia on important pathways of de novo lipogenesis in mouse early and late adipocytes. Hypothesis: Hypoxia affects the utilization of carbon sources for de novo lipogenesis differently in early and late adipocytes. Methods: Mouse 3T3-L1 cells were differentiated into adipocytes for 7 days - early adipocytes (EA) or 14 days - late adipocytes (LA). The cells were cultured in gas-permeable cultureware allowing exposure to sustained oxygen levels of 21% O2 or 4% O2. [13C-5]-glutamine (2.5mM) was added to culture media for 7 and 14 days to assess 13C incorporation to newly synthesized lipids via rTCA and [13C-1]-glutamine (2.5mM) was added to media for 24h to assess 13C incorporation to rTCA metabolites. The 13C incorporation studies were analyzed via gas chromatography-mass spectrometry. The contribution of glucose and acetate to de novo lipogenesis was assessed using [14C]-glucose and [14C]-acetate (both 0.2 μCi) provided in culture media for 2h at the end of experiments. Subsequently, radioactivity in extracted lipids was measured via scintillation counter. Statistical significance was assessed by 2-way ANOVA followed by Tukey's test. Data are presented as means ± SD, N=9. Data Hypoxia had no effect on lipid accumulation in EA, lipid accumulation in LA was increased by 134,41% vs control. The 13C incorporation to lipids was increased in EA by 42,2% vs control and by 13,33% vs LA. The 13C incorporation in citrate was increased by 8,71%, in malate by 9,58% in EA vs control, in LA the incorporation remained unchanged. The [14C]-glucose incorporation to lipids was elevated in EA vs control by 209,98% and EA vs LA by 60,02%. The [14C]-acetate incorporation to lipids was increased in EA by 198,43% vs control and decreased by 45,13% vs LA. Differences are statistically significant (p 14C-glucose incorporation. In LA the rTCA and 14C-glucose incorporation were reduced to the control level and the contribution of acetate was increased. Conclusion: Hypoxia modified metabolic pathways in maturating adipocytes leading to increased de novo lipogenesis and thus hypertrophic mature adipocytes. Project was supported by Grant Agency of the Charles University project GAUK 294822 and by grant AZV project NU21-01-00259 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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- 2023
20. Visceral Fat Accumulation Is Related to Impaired Pancreatic Blood Perfusion and Beta-Cell Dysfunction in Obese Women
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Andrea Plihalova, Michal Anděl, Jiří Weichet, Jan Havlik, Jan Gojda, Jana Potockova, Jan Polak, and Radka Szotkowská
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Blood Glucose ,medicine.medical_specialty ,Medicine (miscellaneous) ,Intra-Abdominal Fat ,Body Mass Index ,Insulin resistance ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Insulin ,Obesity ,Prediabetes ,Pancreas ,Nutrition and Dietetics ,business.industry ,Area under the curve ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,medicine.disease ,Metformin ,Perfusion ,medicine.anatomical_structure ,Endocrinology ,Diabetes Mellitus, Type 2 ,Female ,Insulin Resistance ,business ,medicine.drug - Abstract
Aims/Hypothesis: Beta-cell failure plays a fundamental role in type 2 diabetes mellitus (T2DM) development. It has been shown that the beta-cells are among the most sensitive to hypoxia. We aimed to analyze whether decrease in pancreatic perfusion relates to 1/decline in beta-cell function and 2/visceral fat accumulation in patients with T2DM. Methods: Fifteen women with T2DM on metformin therapy alone and fifteen women of comparable age and BMI without prediabetes/diabetes were cross-sectionally examined: clinical and anthropometric examination, fast sampled intravenous glucose tolerance test (FSIVGTT), dynamic contrast-enhanced magnetic resonance imaging to assess pancreatic perfusion (area under the curve of postcontrast saturation, AUCTSIC), and visceral adiposity (VAT, calculated from transverse sections at the level L2–L5 vertebrae). Results: Pancreatic blood perfusion (AUCTSIC) did not differ between groups (p = 0.273), but it negatively correlated with BMI (r = −0.434, p = 0.017), WHR (r = −0.411, p = 0.024), and VAT (r = −0.436, p = 0.016) in both groups. Moreover, AUCTSIC in the head of the pancreas negatively correlated with the level of fasting glycemia (r = −0.401, p = 0.028) and HOMA-IR (r = −0.376, p = 0.041). Discussion/Conclusion: We showed that decreased pancreatic perfusion did not relate to beta-cell dysfunction in early stages of T2DM development, but it was related to VAT, insulin resistance, and higher fasting glycemia. Furthermore, lower pancreatic perfusion was related to VAT, insulin resistance, and higher fasting glycemia.
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- 2021
21. The impact of iron coagulant on the behavior and biochemistry of freshwater mussels Anodonta cygnea and Unio tumidus during lake restoration
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Agnieszka Drewek, Michał Rybak, Kinga Drzewiecka, Przemysław Niedzielski, Jan Polak, and Piotr Klimaszyk
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Lakes ,Environmental Engineering ,Unio ,Iron ,Animals ,General Medicine ,Hydrogen Peroxide ,Management, Monitoring, Policy and Law ,Waste Management and Disposal ,Anodonta ,Ecosystem - Abstract
Iron (Fe) treatment is one of the most commonly used methods to restore eutrophic lakes and reservoirs. The Fe-based coagulants dosage results in an almost immediate improvement in water quality at a relatively low cost. However, the effects of the application of coagulants are not always predictable, and the scale of the risks is not fully understood. The dosage of coagulants changes the chemical and physical properties of water, thereby affecting aquatic biocenoses. In this study, several laboratory experiments were conducted to evaluate the effects of Fe-based coagulant dosage on two bivalves species: Anodonta anatina and Unio tumidus. Their ability to efficiently filter water and reduce seston makes them a key component of aquatic ecosystems in terms of maintaining proper ecological health and stable functioning. Behavioral response, biochemical parameters, and body chemistry changes in mussels exposed to different doses of coagulant were surveyed. A dose-dependent reduction in filtration activity of both species was observed. As early as 10 g Fe m
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- 2022
22. Przedmioty wirtualne – składnik naszego świata
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Paweł Jan Polak
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lcsh:Philosophy (General) ,virtual entities ,philosophy of informatics ,virtuality ,lcsh:B1-5802 - Abstract
Recenzja książki: Bondecka-Krzykowska I., Brzeziński K.M., Bulińska-Stangrecka H., i in., Przedmioty wirtualne, P. Stacewicz, B. Skowron (red.), Oficyna Wydawnicza Politechniki Warszawskiej, Warszawa 2019, ss. 135.
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- 2020
23. Intermittent Hypoxia Stimulates Lipolysis, But Inhibits Differentiation and De Novo Lipogenesis in 3T3-L1 Cells
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Michal Koc, Martin Weiszenstein, Martina Musutova, and Jan Polak
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medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,3T3-L1 Cells ,030209 endocrinology & metabolism ,Intermittent hypoxia ,Context (language use) ,Plasma levels ,030204 cardiovascular system & hematology ,medicine.disease ,Obstructive sleep apnea ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,chemistry ,Internal medicine ,Adipocyte ,Lipogenesis ,Internal Medicine ,medicine ,Lipolysis ,business - Abstract
Background: Exposure to intermittent hypoxia (IH) may play a role in the development of metabolic impairments in the context of obstructive sleep apnea syndrome, probably by elevated plasma levels ...
- Published
- 2020
24. The Efficient Trabecular Bone Remodeling Numerical Tool Enabling Multiple Load Case Simulation
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Jan Polak and Michał Nowak
- Published
- 2022
25. Iron Coagulant Water Treatment: The Impact on Behavior and Biochemistry of Freshwater Mussels Anodonta Cygnea and Unio Tumidus
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Agnieszka Drewek, Michał Rybak, Kinga Drzewiecka, Przemysław Niedzielski, Jan Polak, and Piotr Klimaszyk
- Published
- 2022
26. Characterization of Individualized Glycemic Excursions during a Standardized Bout of Hypoglycemia-Inducing Exercise and Subsequent Hypoglycemia Treatment—A Pilot Study
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Marek Brabec, Marisa A. Nunes, Juraj Michalec, Jana Urbanová, Arian Taniwall, Matthew Campbell, Jan Brož, Ludmila Brunerová, Vojtěch Berka, Jan Polak, Denisa Janíčková Žďárská, and Dario Rahelić
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Adult ,Blood Glucose ,Male ,type 1 diabetes ,Administration, Oral ,Pilot Projects ,Hypoglycemia ,Target heart rate ,Article ,Heart Rate ,medicine ,Humans ,Insulin ,TX341-641 ,Glucose dynamics ,glycemic excursion ,Glycemic ,Type 1 diabetes ,hypoglycemia treatment ,Nutrition and Dietetics ,exercise ,business.industry ,Nutrition. Foods and food supply ,medicine.disease ,hypoglycemia ,insulin therapy ,Bicycling ,Oral ingestion ,Diabetes Mellitus, Type 1 ,Glucose ,Male patient ,Anesthesia ,Heart rate reserve ,business ,Food Science - Abstract
The glycemic response to ingested glucose for the treatment of hypoglycemia following exercise in type 1 diabetes patients has never been studied. Therefore, we aimed to characterize glucose dynamics during a standardized bout of hypoglycemia-inducing exercise and the subsequent hypoglycemia treatment with the oral ingestion of glucose. Ten male patients with type 1 diabetes performed a standardized bout of cycling exercise using an electrically braked ergometer at a target heart rate (THR) of 50% of the individual heart rate reserve, determined using the Karvonen equation. Exercise was terminated when hypoglycemia was reached, followed by immediate hypoglycemia treatment with the oral ingestion of 20 g of glucose. Arterialized blood glucose (ABG) levels were monitored at 5 min intervals during exercise and for 60 min during recovery. During exercise, ABG decreased at a mean rate of 0.11 ± 0.03 mmol/L·min−1 (minimum: 0.07, maximum: 0.17 mmol/L·min−1). During recovery, ABG increased at a mean rate of 0.13 ± 0.05 mmol/L·min−1 (minimum: 0.06, maximum: 0.19 mmol/L·min−1). Moreover, 20 g of glucose maintained recovery from hypoglycemia throughout the 60 min postexercise observation window.
- Published
- 2021
27. Measuring Mitochondrial Substrate Flux in Recombinant Perfringolysin O-Permeabilized Cells
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Zuzana Červinková, Pavla Staňková, Karolína Vaněčková, Jan Polak, Moustafa Elkalaf, and Otto Kucera
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chemistry.chemical_classification ,Cell type ,General Immunology and Microbiology ,General Chemical Engineering ,General Neuroscience ,Bacterial Toxins ,Cell Respiration ,Substrate (chemistry) ,Mitochondrion ,General Biochemistry, Genetics and Molecular Biology ,Mitochondria ,law.invention ,Hemolysin Proteins ,Oxygen Consumption ,Membrane ,Enzyme ,chemistry ,law ,Recombinant DNA ,Biophysics ,Inner mitochondrial membrane ,Flux (metabolism) - Abstract
Mitochondrial substrate flux is a distinguishing characteristic of each cell type, and changes in its components such as transporters, channels, or enzymes are involved in the pathogenesis of several diseases. Mitochondrial substrate flux can be studied using intact cells, permeabilized cells, or isolated mitochondria. Investigating intact cells encounters several problems due to simultaneous oxidation of different substrates. Besides, several cell types contain internal stores of different substrates that complicate results interpretation. Methods such as mitochondrial isolation or using permeabilizing agents are not easily reproducible. Isolating pure mitochondria with intact membranes in sufficient amounts from small samples is problematic. Using non-selective permeabilizers causes various degrees of unavoidable mitochondrial membrane damage. Recombinant perfringolysin O (rPFO) was offered as a more appropriate permeabilizer, thanks to its ability to selectively permeabilize plasma membrane without affecting mitochondrial integrity. When used in combination with microplate respirometry, it allows testing the flux of several mitochondrial substrates with enough replicates within one experiment while using a minimal number of cells. In this work, the protocol describes a method to compare mitochondrial substrate flux of two different cellular phenotypes or genotypes and can be customized to test various mitochondrial substrates or inhibitors.
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- 2021
28. Wychodzenie z sarmackiej kopalni, czyli teologia nauki w działaniu
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Paweł Jan Polak
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cathegory theory in theology ,lcsh:Philosophy (General) ,G.W. Leibniz ,lcsh:B1-5802 ,paraconsistent logics ,theology of science - Abstract
Recenzja książki: Michał Heller, Ważniejsze niż Wszechświat, Copernicus Center Press, Kraków 2018, ss. 128.
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- 2019
29. Nauka w oczach erudytów
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Paweł Jan Polak
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history of science ,philosophy of science ,lcsh:Philosophy (General) ,Leibniz Gottfried Wilhelm ,Kochański Adam Adamandy ,lcsh:B1-5802 ,correspondence - Abstract
Recenzja książki: Adam Adamandy Kochański, Gottfried Wilhelm Leibniz, Korespondencja Adama Adamandego Kochańskiego i Gottfrieda Wilhelma Leibniza z lat 1670-1698, D. Sieńko (tłum.), wyd. Muzeum Pałacu Króla Jana III w Wilanowie, Warszawa 2019, ss. 256.
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- 2019
30. Limited Knowledge of Safe Driving Practice among Drivers with Diabetes in Armenia: Association with Greater Risk of Motor Vehicle Accidents
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Jan Brož, Katarina Halčiakova, Brian M. Frier, Zhanna Ghazaryan, Lilit Petrosyan, Jan Polak, Marek Brabece, Elena Aghajanova, Denisa Janíčková Žďárská, and Greta Muradyan
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Safe driving ,business.industry ,02 engineering and technology ,Hypoglycemia ,medicine.disease ,Road traffic accident ,Vehicle accident ,020204 information systems ,Diabetes mellitus ,Environmental health ,0202 electrical engineering, electronic engineering, information engineering ,medicine ,Lack of knowledge ,business ,human activities ,Road traffic - Abstract
Aims: The aims of the study were to assess the degree of knowledge and adherence to the recommended safe practice for driving and the risk of road traffic accidents among people with diabetes mellitus in Armenia. Methods: A total of 628 respondents, including 200 drivers, out of 641 consecutive attendees at six diabetes clinics, participated in the survey. A modified British questionnaire on driving and diabetes was used to obtain the relevant data. The information from all 103 drivers treated with insulin and 73 taking sulfonylureas was reviewed. Results: The study revealed that of 176 insulin and sulfonylurea-treated drivers, 161 (91.5%) had never received any advice about safe driving practices. Among the drivers, 156 (88.6%) never measured their blood glucose before, or during driving. The survey revealed that 86 (51.2%) of 168 patients had a history of at least one motor vehicle accident within the previous 5 years. The average road traffic accident rate per person/year was 0.21. Conclusions: The study revealed a lack of knowledge among drivers with diabetes treated with insulin or sulfonylureas concerning recommended safe practices for driving. This was associated with significant hypoglycemia while driving and an elevated rate of road traffic accidents.
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- 2019
31. Hypoxia Induces Saturated Fatty Acids Accumulation and Reduces Unsaturated Fatty Acids Independently of Reverse Tricarboxylic Acid Cycle in L6 Myotubes
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Lukas Vacek, Ales Dvorak, Kamila Bechynska, Vit Kosek, Moustafa Elkalaf, Minh Duc Trinh, Ivana Fiserova, Katerina Pospisilova, Lucie Slovakova, Libor Vitek, Jana Hajslova, and Jan Polak
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Endocrinology, Diabetes and Metabolism ,Citric Acid Cycle ,Fatty Acids ,Muscle Fibers, Skeletal ,Fatty Acids, Unsaturated ,Humans ,Hypoxia - Abstract
Obstructive sleep apnea syndrome, characterized by repetitive episodes of tissue hypoxia, is associated with several metabolic impairments. Role of fatty acids and lipids attracts attention in its pathogenesis for their metabolic effects. Parallelly, hypoxia-induced activation of reverse tricarboxylic acid cycle (rTCA) with reductive glutamine metabolism provides precursor molecules for de novo lipogenesis. Gas-permeable cultureware was used to culture L6-myotubes in chronic hypoxia (12%, 4% and 1% O2) with 13C labelled glutamine and inhibitors of glutamine uptake or rTCA-mediated lipogenesis. We investigated changes in lipidomic profile, 13C appearance in rTCA-related metabolites, gene and protein expression of rTCA-related proteins and glutamine transporters, glucose uptake and lactate production. Lipid content increased by 308% at 1% O2, predominantly composed of saturated fatty acids, while triacylglyceroles containing unsaturated fatty acids and membrane lipids (phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositol) decreased by 20-70%. rTCA labelling of malate, citrate and 2-hydroxyglutarate increased by 4.7-fold, 2.2-fold and 1.9-fold in 1% O2, respectively. ATP-dependent citrate lyase inhibition in 1% O2 decreased lipid amount by 23% and increased intensity of triacylglyceroles containing unsaturated fatty acids by 56-80%. Lactate production increased with hypoxia. Glucose uptake dropped by 75% with progression of hypoxia from 4% to 1% O2. Protein expression remained unchanged. Altogether, hypoxia modified cell metabolism leading to lipid composition alteration and rTCA activation.
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- 2021
32. Does PAD and microcirculation status impact the tissue availability of intravenously administered antibiotics in patients with infected diabetic foot? Results of the DFIATIM substudy
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Vladimíra Fejfarová, Radka Jarošíková, Simona Antalová, Jitka Husáková, Veronika Wosková, Pavol Beca, Jakub Mrázek, Petr Tůma, Jan Polák, Michal Dubský, Dominika Sojáková, Věra Lánská, and Martin Petrlík
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diabetic foot ,antibiotic ,infection ,microdialysis ,peripheral arterial disease ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Aims/hypothesisThe aim of this substudy (Eudra CT No:2019-001997-27)was to assess ATB availability in patients with infected diabetic foot ulcers(IDFUs)in the context of microcirculation and macrocirculation status.MethodsFor this substudy, we enrolled 23 patients with IDFU. Patients were treated with boluses of amoxicillin/clavulanic acid(AMC)(12patients) or ceftazidime(CTZ)(11patients). After induction of a steady ATB state, microdialysis was performed near the IDFU. Tissue fluid samples from the foot and blood samples from peripheral blood were taken within 6 hours. ATB potential efficacy was assessed by evaluating the maximum serum and tissue ATB concentrations(Cmax and Cmax-tissue)and the percentage of time the unbound drug tissue concentration exceeds the minimum inhibitory concentration (MIC)(≥100% tissue and ≥50%/60% tissue fT>MIC). Vascular status was assessed by triplex ultrasound, ankle–brachial and toe–brachial index tests, occlusive plethysmography comprising two arterial flow phases, and transcutaneous oxygen pressure(TcPO2).ResultsFollowing bolus administration, the Cmax of AMC was 91.8 ± 52.5 μgmL-1 and the Cmax-tissue of AMC was 7.25 ± 4.5 μgmL-1(PMIC levels exceeding 50% and 60%, respectively. We observed positive correlations between both Cmax-tissue and AUCtissue and arterial flow. Specifically, the correlation coefficient for the first phase was r=0.42; (P=0.045), and for the second phase, it was r=0.55(P=0.01)and r=0.5(P=0.021).ConclusionsBactericidal activity proved satisfactory in only half to two-thirds of patients with IDFUs, an outcome that appears to correlate primarily with arterial flow.
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- 2024
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33. Interaction of Diet/Lifestyle Intervention and TCF7L2 Genotype on Glycemic Control and Adiposity among Overweight or Obese Adults: Big Data from Seven Randomized Controlled Trials Worldwide
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Matti Uusitupa, Jaakko Tuomilehto, Liana C Del Gobbo, Dominique Langin, Torben Hansen, Lu Qi, Vanessa D. de Mello, Jan Polak, Dolores Corella, Mathilde Svendstrup, Markku Laakso, Jordi Salas-Salvadó, Miguel Ángel Martínez-González, Montserrat Cofán, Alena Stancacova, Wenjie Ma, Dianjianyi Sun, Wenxiu Wang, Tao Huang, Gabby B. Hul, Zhe Fang, Jean-Michel Oppert, Peter Arner, J. Alfredo Martínez, Jörg Hager, Zhenhuang Zhuang, Oluf Pedersen, Sujatha Rajaram, Thorkild I. A. Sørensen, Meng Gao, Arne Astrup, Joan Sabaté, Yoriko Heianza, Wim H. M. Saris, Jaana Lindström, Emilio Ros, and Christopher D. Gardner
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medicine.medical_specialty ,endocrine system diseases ,business.industry ,Computer applications to medicine. Medical informatics ,R858-859.7 ,nutritional and metabolic diseases ,Overweight ,law.invention ,Randomized controlled trial ,law ,Internal medicine ,Genotype ,Lifestyle intervention ,Medicine ,medicine.symptom ,business ,TCF7L2 ,Glycemic - Abstract
Objective . The strongest locus which associated with type 2 diabetes (T2D) by the common variant rs7903146 is the transcription factor 7-like 2 gene ( TCF7L2 ). We aimed to quantify the interaction of diet/lifestyle interventions and the genetic effect of TCF7L2 rs7903146 on glycemic traits, body weight, or waist circumference in overweight or obese adults in several randomized controlled trials (RCTs). Methods . From October 2016 to May 2018, a large collaborative analysis was performed by pooling individual-participant data from 7 RCTs. These RCTs reported changes in glycemic control and adiposity of the variant rs7903146 after dietary/lifestyle-related interventions in overweight or obese adults. Gene treatment interaction models which used the genetic effect encoded by the allele dose and common covariates were applicable to individual participant data in all studies. Results . In the joint analysis, a total of 7 eligible RCTs were included ( n = 4,114 ). Importantly, we observed a significant effect modification of diet/lifestyle-related interventions on the TCF7L2 variant rs7903146 and changes in fasting glucose. Compared with the control group, diet/lifestyle interventions were related to lower fasting glucose by -3.06 (95% CI, -5.77 to -0.36) mg/dL (test for heterogeneity and overall effect: I 2 = 45.1 % , p < 0.05 ; z = 2.20 , p = 0.028 ) per one copy of the TCF7L2 T risk allele. Furthermore, regardless of genetic risk, diet/lifestyle interventions were associated with lower waist circumference. However, there was no significant change for diet/lifestyle interventions in other glycemic control and adiposity traits per one copy of TCF7L2 risk allele. Conclusions . Our findings suggest that carrying the TCF7L2 T risk allele may have a modestly greater benefit for specific diet/lifestyle interventions to improve the control of fasting glucose in overweight or obese adults.
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- 2021
34. Estimation of Blood Glucose Concentration During Endurance Sports
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Jan Brož, Fred Godtliebsen, Stig Uteng, Jan Polak, and Giovanni Sebastiani
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Estimation ,business.industry ,Statistics ,Biomedical Engineering ,Medicine ,Bioengineering ,General Medicine ,business ,VDP::Matematikk og Naturvitenskap: 400::Matematikk: 410 ,General Biochemistry, Genetics and Molecular Biology ,VDP::Mathematics and natural science: 400::Mathematics: 410 - Abstract
In this paper, we describe a new statistical approach to estimate blood glucose concentration along time during endurance sports based on measurements of glucose concentration in subcutaneous interstitial tissue. The final goal is the monitoring of glucose concentration in blood to maximize performance in endurance sports. Blood glucose concentration control during and after aerobic physical activity could also be useful to reduce the risk of hypoglycemia in type 1 diabetes mellitus subjects. By means of a low invasive technology known as "continuous glucose monitoring", glucose concentration in subcutaneous interstitial tissue can now be measured every five minutes. However, it can be expressed as function of blood glucose concentration along time by means of a convolution integral equation. In the training phase of the proposed approach, based on measurements of glucose concentration in both artery and subcutaneous interstitial tissue during physical activity, the parameters of the convolution kernel are estimated. Then, given a new subject performing aerobic physical activity, a deconvolution problem is solved to estimate glucose concentration in blood from continuous glucose monitoring measurements
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- 2020
35. Intermittent Hypoxia Stimulates Lipolysis, But Inhibits Differentiation and
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Martina, Musutova, Martin, Weiszenstein, Michal, Koc, and Jan, Polak
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Gene Expression Profiling ,Lipogenesis ,Lipolysis ,Citric Acid Cycle ,Cell Differentiation ,Cell Hypoxia ,Kinetics ,Mice ,Oxygen Consumption ,Acetyl Coenzyme A ,3T3-L1 Cells ,Adipocytes ,Animals ,Humans ,Glycolysis ,Triglycerides - Published
- 2020
36. Hypoxia modulates effects of fatty acids on human pancreatic [beta]-cells
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Jan Kovar, Jan Polak, Jan Šrámek, and Vlasta Němcová-Fürstová
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medicine.medical_specialty ,Endocrinology ,Chemistry ,Internal medicine ,Pancreatic beta Cells ,medicine ,Hypoxia (medical) ,medicine.symptom - Published
- 2019
37. An innovative intermittent hypoxia model for cell cultures allowing fast P<scp>o</scp>2 oscillations with minimal gas consumption
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Anne Briançon-Marjollet, Mélanie Minoves, Brigitte Gonthier, Jean-Louis Pépin, Jessica Morand, Diane Godin-Ribuot, Morgane Chatard, Emeline Lemarié, Jan Polak, Frédéric Perriot, Jean-Baptiste Menut, Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire (HP2 ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Système Nerveux Autonome - Epidémiologie, Physiologie, Ingénierie, Santé (SNA-EPIS), Université Jean Monnet - Saint-Étienne (UJM)-Centre Hospitalier Universitaire de Saint-Etienne, Charles University [Prague] (CU), Briançon-Marjollet, Anne, Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), and Université Jean Monnet [Saint-Étienne] (UJM)-Centre Hospitalier Universitaire de Saint-Etienne
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0301 basic medicine ,medicine.medical_specialty ,[SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Physiology ,chemistry.chemical_element ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,030204 cardiovascular system & hematology ,Biology ,Blood–brain barrier ,Oxygen ,Andrology ,03 medical and health sciences ,0302 clinical medicine ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,medicine ,Functional studies ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,Tumor hypoxia ,Intermittent hypoxia ,Cell Biology ,Hypoxia (medical) ,Surgery ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Cell culture ,medicine.symptom ,Gas consumption - Abstract
Performing hypoxia-reoxygenation cycles in cell culture with a cycle duration accurately reflecting what occurs in obstructive sleep apnea (OSA) patients is a difficult but crucial technical challenge. Our goal was to develop a novel device to expose multiple cell culture dishes to intermittent hypoxia (IH) cycles relevant to OSA with limited gas consumption. With gas flows as low as 200 ml/min, our combination of plate holders with gas-permeable cultureware generates rapid normoxia-hypoxia cycles. Cycles alternating 1 min at 20% O2 followed by 1 min at 2% O2 resulted in Po2 values ranging from 124 to 44 mmHg. Extending hypoxic and normoxic phases to 10 min allowed Po2 variations from 120 to 25 mmHg. The volume of culture medium or the presence of cells only modestly affected the Po2 variations. In contrast, the nadir of the hypoxia phase increased when measured at different heights above the membrane. We validated the physiological relevance of this model by showing that hypoxia inducible factor-1α expression was significantly increased by IH exposure in human aortic endothelial cells, murine breast carcinoma (4T1) cells as well as in a blood-brain barrier model (2.5-, 1.5-, and 6-fold increases, respectively). In conclusion, we have established a new device to perform rapid intermittent hypoxia cycles in cell cultures, with minimal gas consumption and the possibility to expose several culture dishes simultaneously. This device will allow functional studies of the consequences of IH and deciphering of the molecular biology of IH at the cellular level using oxygen cycles that are clinically relevant to OSA.
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- 2017
38. Increased Incretin But Not Insulin Response after Oral versus Intravenous Branched Chain Amino Acids
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Andrea Plihalova, Michal Anděl, Jana Potockova, Jan Polak, Petr Tůma, Jan Gojda, and Radka Straková
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Adult ,Blood Glucose ,Male ,0301 basic medicine ,endocrine system ,medicine.medical_specialty ,medicine.medical_treatment ,Administration, Oral ,Medicine (miscellaneous) ,Incretin ,030209 endocrinology & metabolism ,Gastric Inhibitory Polypeptide ,Placebo ,Incretins ,Glucagon ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Glucagon-Like Peptide 1 ,Leucine ,Valine ,Internal medicine ,Humans ,Insulin ,Medicine ,Isoleucine ,030109 nutrition & dietetics ,Nutrition and Dietetics ,C-Peptide ,Dose-Response Relationship, Drug ,business.industry ,Glucagon-like peptide-1 ,Endocrinology ,Administration, Intravenous ,business ,Amino Acids, Branched-Chain ,hormones, hormone substitutes, and hormone antagonists - Abstract
Background/Aims: Branched chain amino acids (BCAAs) are known to exert an insulinotropic effect. Whether this effect is mediated by incretins (glucagon like peptide 1 [GLP-1] or glucose-dependent insulinotropic peptide [GIP]) is not known. The aim of this study was to show whether an equivalent dose of BCAA elicits a greater insulin and incretin response when administered orally than intravenously (IV). Methods: Eighteen healthy, male subjects participated in 3 tests: IV application of BCAA solution, oral ingestion of BCAA and placebo in an equivalent dose (30.7 ± 1.1 g). Glucose, insulin, C-peptide, glucagon, GLP-1, GIP, valine, leucine and isoleucine concentrations were measured. Results: Rise in serum BCAA was achieved in both BCAA tests, with incremental areas under the curve (iAUC) being 2.1 times greater for IV BCAA compared with those of the oral BCAA test (p < 0.0001). Oral and IV BCAA induced comparable insulin response greater than placebo (240 min insulin iAUC: oral 3,411 ± 577 vs. IV 2,361 ± 384 vs. placebo 961.2 ± 175 pmol/L, p = 0.0006). Oral BCAA induced higher GLP-1 (p < 0.0001) and GIP response (p < 0.0001) compared with the IV or placebo. Glucose levels declined significantly (p < 0.001) in the same pattern during both BCAA tests with no change in the placebo group. Conclusions: An equivalent dose of BCAA elicited a comparable insulin and greater incretin response when administered orally and not when administered through IV. We conclude that insulinotropic effects of BCAA are partially incretin dependent.
- Published
- 2017
39. Hypoxia Modulates Effects of Fatty Acids on NES2Y Human Pancreatic β-cells
- Author
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Jan Šrámek, Vlasta Němcová-Fürstová, Jan Kovář, and Jan Polak
- Subjects
0301 basic medicine ,CD36 ,lcsh:Chemistry ,chemistry.chemical_compound ,0302 clinical medicine ,Insulin-Secreting Cells ,lcsh:QH301-705.5 ,Spectroscopy ,Caspase ,biology ,NES2Y ,Chemistry ,Communication ,Fatty Acids ,apoptosis ,General Medicine ,fatty acid transporters ,Endoplasmic Reticulum Stress ,Computer Science Applications ,caspases ,030220 oncology & carcinogenesis ,ER stress ,Signal Transduction ,medicine.medical_specialty ,Cell type ,pancreatic β-cells ,Cell Survival ,Catalysis ,Cell Line ,Inorganic Chemistry ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,hypoxia-inducible factor 1α ,Cell Proliferation ,Cluster of differentiation ,hypoxia ,Endoplasmic reticulum ,Organic Chemistry ,Oleic acid ,030104 developmental biology ,Endocrinology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Apoptosis ,biology.protein ,Unfolded protein response ,Biomarkers - Abstract
Saturated fatty acids (FAs) induce apoptosis in the human pancreatic NES2Y β-cell line while unsaturated FAs have nearly no detrimental effect. Moreover, unsaturated FAs are capable of inhibiting the pro-apoptotic effect of saturated FAs. Hypoxia is also known to have deleterious effects on β-cells function and viability. In the present study, we have tested the modulatory effect of hypoxia on the effect of FAs on the growth and viability of the human pancreatic NES2Y β-cells. This study represents the first study testing hypoxia effect on effects of FAs in pancreatic β-cells as well as in other cell types. We showed that hypoxia increased the pro-apoptotic effect of saturated stearic acid (SA). Endoplasmic reticulum stress signaling seemed to be involved while redistribution of FA transporters fatty acid translocase/cluster of differentiation 36 (FAT/CD36) and fatty acid-binding protein (FABP) do not seem to be involved in this effect. Hypoxia also strongly decreased the protective effect of unsaturated oleic acid (OA) against the pro-apoptotic effect of SA. Thus, in the presence of hypoxia, OA was unable to save SA-treated β-cells from apoptosis induction. Hypoxia itself had only a weak detrimental effect on NES2Y cells. Our data suggest that hypoxia could represent an important factor in pancreatic β-cell death induced and regulated by FAs and thus in the development of type 2 diabetes mellitus.
- Published
- 2019
40. Screening for obstructive sleep apnea syndrome in patients with type 2 diabetes mellitus: a prospective study on sensitivity of Berlin and STOP-Bang questionnaires
- Author
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Andrea Plihalova, M. Pretl, Katerina Westlake, Zuzana Lattova, and Jan Polak
- Subjects
Male ,Pediatrics ,medicine.medical_specialty ,Polysomnography ,Population ,Comorbidity ,Sensitivity and Specificity ,Severity of Illness Index ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Risk Factors ,Surveys and Questionnaires ,Diabetes mellitus ,Humans ,Mass Screening ,Medicine ,In patient ,Prospective Studies ,Risk factor ,education ,Prospective cohort study ,Aged ,Cause of death ,Analysis of Variance ,Sleep Apnea, Obstructive ,education.field_of_study ,business.industry ,Type 2 Diabetes Mellitus ,General Medicine ,Middle Aged ,medicine.disease ,Obstructive sleep apnea ,Diabetes Mellitus, Type 2 ,030228 respiratory system ,Female ,business ,030217 neurology & neurosurgery - Abstract
Background Obstructive sleep apnea (OSA) is highly prevalent in patients with Type 2 diabetes mellitus representing an additional risk factor for already increased cardiovascular mortality. As cardiovascular diseases are the main cause of death in this population, there is a need to identify patients with moderate to severe OSA indicated for treatment. We aimed to evaluate the performance of the Berlin, STOP, and STOP-Bang screening questionnaires in a population of patients with Type 2 diabetes mellitus. Methods 294 consecutive patients with Type 2 diabetes mellitus filled in the questionnaires and underwent overnight home sleep monitoring using a type IV sleep monitor. Results Severe, moderate, and mild OSA was found in 31 (10%), 61 (21%), and 121 (41%) patients, respectively. The questionnaires showed a similar sensitivity and specificity for AHI ≥ 15: 0.69 and 0.50 for Berlin, 0.65 and 0.49 for STOP, and 0.59 and 0.68 for STOP-Bang. However, the performance of the STOP-Bang questionnaire was different in men vs. women, sensitivity being 0.74 vs. 0.29 (p Conclusions Even the best-performing Berlin questionnaire failed to identify 31% of patients with moderate to severe OSA as being at high risk of OSA, thus preventing them from receiving a correct diagnosis and treatment. Considering that patients with Type 2 diabetes mellitus are at high risk of cardiovascular mortality and also have a high prevalence of moderate to severe OSA, we find screening based on the questionnaires suboptimal and suggest that OSA screening should be performed using home sleep monitoring devices.
- Published
- 2016
41. Adipogenesis, lipogenesis and lipolysis is stimulated by mild but not severe hypoxia in 3T3-L1 cells
- Author
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Michal Koc, Jan Pala, Jan Polak, Martin Weiszenstein, Jan Trnka, Sumeet Gulati, Katerina Westlake, Moustafa Elkalaf, Andrea Plihalova, Antonin Prochazka, and Martina Musutova
- Subjects
0301 basic medicine ,Perilipin-1 ,medicine.medical_specialty ,ATP citrate lyase ,Lipolysis ,Citric Acid Cycle ,Biophysics ,030209 endocrinology & metabolism ,Biology ,Fatty Acid-Binding Proteins ,Biochemistry ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Acetyl Coenzyme A ,3T3-L1 Cells ,Lipid droplet ,Adipocyte ,Internal medicine ,Adipocytes ,medicine ,Animals ,Diacylglycerol O-Acyltransferase ,Molecular Biology ,Triglycerides ,Adipogenesis ,Dose-Response Relationship, Drug ,Triglyceride ,Lipogenesis ,Cell Differentiation ,Lipid Droplets ,Cell Biology ,Sterol Esterase ,Hypoxia (medical) ,Hypoxia-Inducible Factor 1, alpha Subunit ,Cell Hypoxia ,Oxygen ,030104 developmental biology ,Endocrinology ,Gene Expression Regulation ,chemistry ,ATP Citrate (pro-S)-Lyase ,medicine.symptom ,Signal Transduction - Abstract
In-vitro investigation of the effects of hypoxia is limited by physical laws of gas diffusion and cellular O2 consumption, making prolonged exposures to stable O2 concentrations impossible. Using a gas-permeable cultureware, chronic effects of mild and severe hypoxia on triglyceride accumulation, lipid droplet size distribution, spontaneous lipolysis and gene expression of adipocyte-specific markers were assessed. 3T3-L1 cells were differentiated under 20%, 4% or 1% O2 using a gas-permeable cultureware. Triglyceride accumulation, expression of genes characteristic for advanced adipocyte differentiation and involvement of key lipogenesis enzymes were assessed after exposures. Lipogenesis increased by 375% under mild hypoxia, but dropped by 43% in severe hypoxia. Mild, but not severe, hypoxia increased formation of large lipid droplets 6.4 fold and strongly induced gene expression of adipocyte-specific markers. Spontaneous lipolysis increased by 488% in mild, but only by 135% in severe hypoxia. Inhibition of ATP-dependent citrate lyase suppressed hypoxia-induced lipogenesis by 81% and 85%. Activation of HIF inhibited lipogenesis by 59%. Mild, but not severe, hypoxia stimulates lipolysis and promotes adipocyte differentiation, probably through excess of acetyl-CoA originating from tricarboxylic acid cycle independently of HIF activation.
- Published
- 2016
42. The Effect of Hypoxia and Metformin on Fatty Acid Uptake, Storage, and Oxidation in L6 Differentiated Myotubes
- Author
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Moustafa Elkalaf, Jan Kovar, Minh Duc Trinh, Jan Rambousek, Michal Koc, Kamila Balušíková, Beatriz Volckaert, Martin Kalous, Jan Polak, Stanislav Povysil, Jan Trnka, Natálie Klubíčková, Martina Musutova, and František Duška
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,CD36 ,Peroxisome proliferator-activated receptor ,CD36 receptor ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,GW501516 ,03 medical and health sciences ,Endocrinology ,0302 clinical medicine ,Internal medicine ,FFA oxidation ,medicine ,Receptor ,Original Research ,chemistry.chemical_classification ,lcsh:RC648-665 ,biology ,hypoxia ,FFA uptake ,Fatty acid ,free fatty acids ,Hypoxia (medical) ,medicine.disease ,Metformin ,030104 developmental biology ,myotubes ,chemistry ,biology.protein ,medicine.symptom ,metformin ,030217 neurology & neurosurgery ,Intracellular ,medicine.drug - Abstract
Metabolic impairments associated with obstructive sleep apnea syndrome (OSA) are linked to tissue hypoxia, however, the explanatory molecular and endocrine mechanisms remain unknown. Using gas-permeable cultureware, we studied the chronic effects of mild and severe hypoxia on free fatty acid (FFA) uptake, storage, and oxidation in L6 myotubes under 20, 4, or 1% O2. Additionally, the impact of metformin and the peroxisome proliferator-activated receptor (PPAR) β/δ agonist, called GW501516, were investigated. Exposure to mild and severe hypoxia reduced FFA uptake by 37 and 32%, respectively, while metformin treatment increased FFA uptake by 39% under mild hypoxia. GW501516 reduced FFA uptake under all conditions. Protein expressions of CD36 (cluster of differentiation 36) and SCL27A4 (solute carrier family 27 fatty acid transporter, member 4) were reduced by 17 and 23% under severe hypoxia. Gene expression of UCP2 (uncoupling protein 2) was reduced by severe hypoxia by 81%. Metformin increased CD36 protein levels by 28% under control conditions and SCL27A4 levels by 56% under mild hypoxia. Intracellular lipids were reduced by mild hypoxia by 18%, while in controls only, metformin administration further reduced intracellular lipids (20% O2) by 36%. Finally, palmitate oxidation was reduced by severe hypoxia, while metformin treatment reduced non-mitochondrial O2 consumption, palmitate oxidation, and proton leak at all O2 levels. Hypoxia directly reduced FFA uptake and intracellular lipids uptake in myotubes, at least partially, due to the reduction in CD36 transporters. Metformin, but not GW501516, can increase FFA uptake and SCL27A4 expression under mild hypoxia. Described effects might contribute to elevated plasma FFA levels and metabolic derangements in OSA.
- Published
- 2018
43. Diet/Lifestyle Intervention Influences Genetic Effect of TCF7L2 Genotype on Glycemic Control and Adiposity Among 4,114 Individuals Enrolled in Seven Randomized Controlled Trials
- Author
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Jordi Salas-Salvadó, Sujatha Rajaram, Joan Sabaté, Torben Hansen, Yoriko Heianza, Miguel Ángel Martínez-González, Wim H. M. Saris, Matti Uusitupa, Montserrat Cofán, Jörg Hager, Alena Stancacova, Jaakko Tuomilehto, Meng Gao, Dianjianyi Sun, Wenjie Ma, J. Alfredo Martínez, Jaana Lindström, Peter Arner, Liana C Del Gobbo, Markku Laakso, Thorkild I. A. Sørensen, Lu Qi, Jean-Michel Oppert, Tao Huang, Arne Astrup, Oluf Pedersen, Mathilde Svendstrup, Jan Polak, Dolores Corella, Dominique Langin, Gabby B. Hul, Zhe Fang, Vanessa D. de Mello, Christopher D. Gardner, and Emilio Ros
- Subjects
medicine.medical_specialty ,Waist ,business.industry ,Psychological intervention ,Type 2 diabetes ,medicine.disease ,Obesity ,law.invention ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Glucose homeostasis ,business ,TCF7L2 ,Glycemic - Abstract
Background: The transcription factor 7-like 2 gene (TCF7L2) is the strongest locus associated by the variant rs7903146 with type 2 diabetes (T2D) identified to date. Whether diet/lifestyle intervention modifies genetic effect of TCF7L2 variant on glucose homeostasis and adiposity is still controversial. Objective: To quantify the modification effects of the diet/lifestyle interventions on genetic association of TCF7L2 variant rs7903146 with glycemic control and adiposity changes in randomized controlled trials (RCTs). Design A large collaborative analysis of individual-participant data from seven RCTs. Setting RCTs conducted in adults reporting changes in glycemic traits, body weight, or waist circumference by TCF7L2 rs7903146 after dietary/lifestyle-based interventions. Gene-treatment interaction models were fitted to individual participant data from all studies, using allele dose coding for genetic effects and a common set of covariates. Results: We included seven eligible RCTs for the joint analysis (n=4,114 participants). Overall, a significant interaction between TCF7L2 rs7903146 and diet/lifestyle interventions on decrease in fasting glucose was observed. Compared with control, diet/lifestyle interventions reduced fasting glucose by -0.17 (95% CI, -0.32 to -0.02) mmol/L (test for heterogeneity: I2=45.1%, p
- Published
- 2018
44. Effect of Short-Term Hyperglycemia on Adipose Tissue Fluxes of Selected Cytokines In Vivo During Multiple Phases of Diet-Induced Weight Loss in Obese Women
- Author
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Lene Simonsen, Vladimir Stich, Michaela Šiklová, Jan Polak, and Jens Bülow
- Subjects
Adult ,medicine.medical_specialty ,Diet, Reducing ,Diet therapy ,Endocrinology, Diabetes and Metabolism ,food.diet ,medicine.medical_treatment ,Clinical Biochemistry ,Adipose tissue ,Biochemistry ,Proinflammatory cytokine ,Endocrinology ,food ,Weight loss ,Internal medicine ,Weight Loss ,medicine ,Humans ,Obesity ,Serum amyloid A ,business.industry ,Biochemistry (medical) ,Very low calorie diet ,Cytokine ,Adipose Tissue ,Hyperglycemia ,Cytokines ,Female ,medicine.symptom ,business ,Hyperglycemic agent - Abstract
Hyperglycemia is suggested to be one of the drivers of the proinflammatory state observed in obese and diabetic patients.The objectives of the study was to investigate whether sc abdominal adipose tissue (scAT) could be one of the important sources of proinflammatory cytokines released in response to short-term hyperglycemia and whether this secretion capacity could be influenced by weight loss.Output of cytokines and proteins of acute phase from scAT in response to a 3-hours hyperglycemic clamp was evaluated in nine obese women in vivo using Fick's principle. Moreover, the output of cytokines was analyzed during a multiphase dietary intervention consisting of 1 month on a very low-calorie diet and subsequent 5-month weight-stabilization phase.The levels of cytokines and proteins of acute phase [IL-6, IL-8, IL-1 receptor antagonist (IL-1Ra), TNF-α, monocyte chemoattractant protein-1 (MCP-1), serum amyloid A, and C-reactive protein] in arterial and venous plasma were measured during each dietary phase. The insulin sensitivity of scAT in respect to the antilipolytic effect of insulin during the clamp was assessed.Hyperglycemia increased the output of cytokines IL-6, MCP-1, and IL-1Ra from scAT. This effect had a tendency to be reduced after weight loss. The output of other proinflammatory substances from scAT into circulation was not detected. The diet-induced weight loss was associated with the improvement of antilipolytic insulin sensitivity in scAT.The results suggest that short-term hyperglycemia induces an increase of the output of cytokines IL-6, IL-1Ra, and MCP-1 from adipose tissue, and this deleterious hyperglycemia effect may be attenuated by the diet-induced weight reduction. This lowered responsiveness of the inflammation-related system may be an important feature of the weight reduction-induced improvement of the metabolic status of obese prediabetic individuals.
- Published
- 2015
45. The effect of hypoxia and re-oxygenation on adipose tissue lipolysis in COPD patients
- Author
-
Sumeet Gulati, Martina Vasakova, Andrea Plihalova, Isabelle deGlisezinski, Vladimir Stich, Jan Polak, and Hana Bartakova
- Subjects
Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Oxygen inhalation therapy ,Microdialysis ,Epinephrine ,Copd patients ,Lipolysis ,Adipose tissue ,macromolecular substances ,Fatty Acids, Nonesterified ,030204 cardiovascular system & hematology ,Severe copd ,Severity of Illness Index ,Pulmonary Disease, Chronic Obstructive ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Sympathomimetics ,Hypoxia ,business.industry ,Oxygen Inhalation Therapy ,Middle Aged ,Hypoxia (medical) ,Subcutaneous Fat, Abdominal ,respiratory tract diseases ,Surgery ,Endocrinology ,Adipose Tissue ,030228 respiratory system ,cardiovascular system ,Re oxygenation ,Female ,medicine.symptom ,business ,Atrial Natriuretic Factor ,hormones, hormone substitutes, and hormone antagonists - Abstract
Oxygen administration inhibits spontaneous and ANP-stimulated lipolysis in adipose tissue in severe COPD http://ow.ly/ZVg53022Yah
- Published
- 2016
46. An innovative intermittent hypoxia model for cell cultures allowing fast Po
- Author
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Mélanie, Minoves, Jessica, Morand, Frédéric, Perriot, Morgane, Chatard, Brigitte, Gonthier, Emeline, Lemarié, Jean-Baptiste, Menut, Jan, Polak, Jean-Louis, Pépin, Diane, Godin-Ribuot, and Anne, Briançon-Marjollet
- Subjects
Sleep Apnea, Obstructive ,Time Factors ,Cell Culture Techniques ,Endothelial Cells ,Breast Neoplasms ,Equipment Design ,Hypoxia-Inducible Factor 1, alpha Subunit ,Cell Hypoxia ,Culture Media ,Oxygen ,Blood-Brain Barrier ,Cell Line, Tumor ,Animals ,Humans ,Tumor Hypoxia ,Female ,Gases ,Hypoxia - Abstract
Performing hypoxia-reoxygenation cycles in cell culture with a cycle duration accurately reflecting what occurs in obstructive sleep apnea (OSA) patients is a difficult but crucial technical challenge. Our goal was to develop a novel device to expose multiple cell culture dishes to intermittent hypoxia (IH) cycles relevant to OSA with limited gas consumption. With gas flows as low as 200 ml/min, our combination of plate holders with gas-permeable cultureware generates rapid normoxia-hypoxia cycles. Cycles alternating 1 min at 20% O
- Published
- 2017
47. Intermittent Hypoxia Impairs Glucose Homeostasis in C57BL6/J Mice: Partial Improvement with Cessation of the Exposure
- Author
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Clark Undem, Holly McHugh, Luciano F. Drager, Naresh M. Punjabi, Jan Polak, Larissa A. Shimoda, and Vsevolod Y. Polotsky
- Subjects
Blood Glucose ,medicine.medical_specialty ,medicine.medical_treatment ,Carbohydrate metabolism ,Mice ,chemistry.chemical_compound ,Insulin resistance ,Insulin-Secreting Cells ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Homeostasis ,Glucose homeostasis ,Hypoxia ,Sleep Apnea, Obstructive ,Glucose tolerance test ,medicine.diagnostic_test ,Glycogen ,business.industry ,Insulin ,Intermittent hypoxia ,Glucose Tolerance Test ,Hypoxia (medical) ,medicine.disease ,Mice, Inbred C57BL ,Disease Models, Animal ,Oxidative Stress ,Glucose ,Endocrinology ,chemistry ,Intermittent Hypoxia Impairs Glucose Homeostasis ,Neurology (clinical) ,Insulin Resistance ,medicine.symptom ,business - Abstract
Objectives Obstructive sleep apnea is associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Although several studies have suggested that intermittent hypoxia in obstructive sleep apnea may induce abnormalities in glucose homeostasis, it remains to be determined whether these abnormalities improve after discontinuation of the exposure. The objective of this study was to delineate the effects of intermittent hypoxia on glucose homeostasis, beta cell function, and liver glucose metabolism and to investigate whether the impairments improve after the hypoxic exposure is discontinued. Interventions C57BL6/J mice were exposed to 14 days of intermittent hypoxia, 14 days of intermittent air, or 7 days of intermittent hypoxia followed by 7 days of intermittent air (recovery paradigm). Glucose and insulin tolerance tests were performed to estimate whole-body insulin sensitivity and calculate measures of beta cell function. Oxidative stress in pancreatic tissue and glucose output from isolated hepatocytes were also assessed. Results Intermittent hypoxia increased fasting glucose levels and worsened glucose tolerance by 67% and 27%, respectively. Furthermore, intermittent hypoxia exposure was associated with impairments in insulin sensitivity and beta cell function, an increase in liver glycogen, higher hepatocyte glucose output, and an increase in oxidative stress in the pancreas. While fasting glucose levels and hepatic glucose output normalized after discontinuation of the hypoxic exposure, glucose intolerance, insulin resistance, and impairments in beta cell function persisted. Conclusions Intermittent hypoxia induces insulin resistance, impairs beta cell function, enhances hepatocyte glucose output, and increases oxidative stress in the pancreas. Cessation of the hypoxic exposure does not fully reverse the observed changes in glucose metabolism.
- Published
- 2013
48. Screening for Obstructive Sleep Apnea in Type 2 Diabetes Patients – Questionnaires Are Not Good Enough
- Author
-
Jan Polak and Katerina Westlake
- Subjects
medicine.medical_specialty ,Pediatrics ,Opinion ,Endocrinology, Diabetes and Metabolism ,Population ,Type 2 diabetes ,home sleep monitor ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,medicine ,cardiovascular risk factor ,030212 general & internal medicine ,Risk factor ,education ,education.field_of_study ,business.industry ,screening ,STOP Bang questionnaire ,Sleep apnea ,Berlin questionnaire ,Airway obstruction ,medicine.disease ,sleep apnea ,Obesity ,respiratory tract diseases ,Obstructive sleep apnea ,Physical therapy ,type 2 diabetes ,business ,030217 neurology & neurosurgery ,Dyslipidemia - Abstract
The shorter life expectancy of patients with type 2 diabetes caused by cardiovascular and cerebrovascular diseases compels clinicians to make a systematic effort to address traditional cardiovascular risk factors, such as dyslipidemia, hypertension, hyperglycemia, obesity, and smoking. However, another major cardiovascular risk factor substantially influencing the quality and length of life – obstructive sleep apnea syndrome (OSA) – is frequently overlooked. OSA is characterized by a repetitive upper airway obstruction during sleep leading to intermittent hypoxemia and sleep fragmentation. Numerous epidemiological studies have proved that untreated OSA represents an independent risk factor significantly increasing all cause as well as cardiovascular, cerebrovascular, and cancer mortality (1–7). The importance of OSA is underscored by its considerable prevalence ranging from 5 to 10% in the general population and is even higher in the population of type 2 diabetes patients where a prevalence of ~70% was reported (8–10). Furthermore, ~90% of all subjects suffering from moderate or severe OSA remain undiagnosed (11).
- Published
- 2016
49. Inhibition of Lipolysis Ameliorates Diabetic Phenotype in a Mouse Model of Obstructive Sleep Apnea
- Author
-
Michal Koc, Martin Weiszenstein, Jan Polak, Larissa A. Shimoda, and Ondrej Seda
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Male ,Acipimox ,medicine.medical_specialty ,medicine.medical_treatment ,Lipolysis ,Clinical Biochemistry ,Type 2 diabetes ,Diabetes Mellitus, Experimental ,03 medical and health sciences ,chemistry.chemical_compound ,Insulin resistance ,Diabetes mellitus ,Adipocyte ,Internal medicine ,medicine ,Adipocytes ,Animals ,Insulin ,Hypoxia ,Molecular Biology ,Original Research ,Adiposity ,Sleep Apnea, Obstructive ,business.industry ,Fatty Acids ,Intermittent hypoxia ,Cell Biology ,medicine.disease ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Glucose ,Phenotype ,chemistry ,Gene Expression Regulation ,Pyrazines ,business ,medicine.drug ,Signal Transduction - Abstract
Obstructive sleep apnea (OSA) is associated with insulin resistance, glucose intolerance, and type 2 diabetes. Causal mechanisms mediating this association are not well defined; however, augmented lipolysis in adipose might be involved. Here, we investigated the effect of acipimox treatment (lipolysis inhibitor) on glucose tolerance and insulin sensitivity in mice exposed to intermittent hypoxia (IH). C57BL6/J mice were exposed for 14 days to IH or control conditions. IH was created by decreasing the fraction of inspired oxygen from 20.9 to 6.5%, 60 times/h. Control exposure was air (fraction of inspired oxygen, 20.9%) delivered at an identical flow rate. Acipimox was provided in drinking water (0.5 g/ml) during exposures. After exposures, intraperitoneal insulin (0.5 IU/kg) and glucose (1 g/kg) tolerance tests were performed, and primary adipocytes were isolated for lipolysis experiments. IH elevated fasting glucose by 51% and worsened glucose tolerance and insulin sensitivity by 33 and 102%, respectively. In parallel, IH increased spontaneous lipolysis by 264%, and reduced epididymal fat mass by 15% and adipocyte size by 8%. Acipimox treatment prevented IH-induced lipolysis and increased epididymal fat mass and adipocyte size by 19 and 10%, respectively. Acipimox fully prevented IH-induced impairments in fasting glycemia, glucose tolerance, and insulin sensitivity. For all reported results, P less than 0.05 was considered significant. Augmented lipolysis contributes to insulin resistance and glucose intolerance observed in mice exposed to IH. Acipimox treatment ameliorated the metabolic consequences of IH and might represent a novel treatment option for patients with obstructive sleep apnea.
- Published
- 2016
50. Mitochondrial Probe Methyltriphenylphosphonium (TPMP) Inhibits the Krebs Cycle Enzyme 2-Oxoglutarate Dehydrogenase
- Author
-
Jan Polak, Petr Tůma, Moustafa Elkalaf, Martin Weiszenstein, and Jan Trnka
- Subjects
0301 basic medicine ,Metabolic Processes ,Physiology ,Cell Membranes ,lcsh:Medicine ,Mitochondrion ,Biochemistry ,chemistry.chemical_compound ,Onium Compounds ,Glutamate Dehydrogenase ,Malate Dehydrogenase ,Medicine and Health Sciences ,Enzyme Inhibitors ,lcsh:Science ,Energy-Producing Organelles ,chemistry.chemical_classification ,Membrane potential ,Membrane Potential, Mitochondrial ,Multidisciplinary ,Trityl Compounds ,Ketones ,Isocitrate Dehydrogenase ,Mitochondria ,Enzymes ,Electrophysiology ,Chemistry ,Mitochondrial matrix ,Physical Sciences ,Cellular Structures and Organelles ,Oxidoreductases ,Research Article ,Pyruvate ,Cell Physiology ,Cellular respiration ,Citric Acid Cycle ,Mixed inhibition ,Pyruvate Dehydrogenase Complex ,Citrate (si)-Synthase ,Biology ,Bioenergetics ,Membrane Potential ,Cell Line ,03 medical and health sciences ,Extracellular ,Animals ,Ketoglutarate Dehydrogenase Complex ,Rats, Wistar ,Muscle, Skeletal ,Dehydrogenases ,030102 biochemistry & molecular biology ,lcsh:R ,Chemical Compounds ,Biology and Life Sciences ,Proteins ,Cell Biology ,Mitochondria, Muscle ,Rats ,Cell Metabolism ,Citric acid cycle ,030104 developmental biology ,Enzyme ,Metabolism ,chemistry ,Enzymology ,lcsh:Q ,Acids - Abstract
Methyltriphenylphosphonium (TPMP) salts have been widely used to measure the mitochondrial membrane potential and the triphenylphosphonium (TPP+) moiety has been attached to many bioactive compounds including antioxidants to target them into mitochondria thanks to their high affinity to accumulate in the mitochondrial matrix. The adverse effects of these compounds on cellular metabolism have been insufficiently studied and are still poorly understood. Micromolar concentrations of TPMP cause a progressive inhibition of cellular respiration in adherent cells without a marked effect on mitochondrial coupling. In permeabilized cells the inhibition was limited to NADH-linked respiration. We found a mixed inhibition of the Krebs cycle enzyme 2-oxoglutarate dehydrogenase complex (OGDHC) with an estimated IC50 3.93 [3.70-4.17] mM, which is pharmacologically plausible since it corresponds to micromolar extracellular concentrations. Increasing the lipophilic character of the used TPP+ compound further potentiates the inhibition of OGDHC activity. This effect of TPMP on the Krebs cycle ought to be taken into account when interpreting observations on cells and mitochondria in the presence of TPP+ derivatives. Compounds based on or similar to TPP+ derivatives may also be used to alter OGDHC activity for experimental or therapeutic purposes.
- Published
- 2016
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