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Objective. Due to insulin resistance and oxidative stress that are associated with type 2 diabetes mellitus (T2DM), T2DM has become a prevalent metabolic disorder that presents various side effects. However, alternative antidiabetic treatment has commonly been used in treating diabetes mellitus in diabetic patients. In our previous studies, bredemolic acid has been reported as an antidiabetic agent that improves glucose uptake, ameliorates insulin resistance, and oxidative stress in the liver, heart, kidney, and skeletal muscle of prediabetic rats. However, these effects have not been validated in vitro. Therefore, this study was aimed to investigate the effects of bredemolic acid on insulin-mediated glucose utilization, lipid peroxidation, and the total antioxidant capacity (TOAC) in palmitic acid-induced insulin-resistant C2C12 skeletal muscle cells in vitro.

Efavirenz, tenofovir, rifampicin, simvastatin, lamotrigine and clarithromycin are known potential mitochondrial toxicants. Mitochondrial toxicity has been reported to disrupt the chain of events in the insulin signalling pathway. Considering the upward trajectory of diabetes mellitus prevalence, studies which seek to uncover probable risk factors for developing diabetes should be encouraged. This study aimed to evaluate the intracellular mechanisms leading to the development of insulin resistance in the presence of various conventional pharmacological agents reported as potential mitochondrial toxicants in skeletal muscle cell line. Differentiated C2C12 preparations were exposed to multiple concentrations of efavirenz, tenofovir, rifampicin, simvastatin, lamotrigine, and clarithromycin, separately. Glucose handling was evaluated by observing the changes in insulin-stimulated glucose uptake and assessing the changes in GLUT4 translocation, GLUT4 expression and Akt expression. The changes in mitochondrial function were evaluated by assessing mitochondrial membrane integrity, cellular ATP production, generation of intracellular reactive oxygen species, expression of tafazzin and quantification of medium malonaldehyde. Insulin stimulated glucose uptake was perturbed in C2C12 pre-treated with potential mitotoxicants. Additionally, ATP synthesis, alterations in mitochondrial membrane potential, excessive accumulation of ROS and malonaldehyde were observed in the presence of potential mitotoxicants. Particularly, we observed suppression of proteins involved in the insulin signalling pathway and maintenance of mitochondrial function namely GLUT4, Akt and tafazzin. Mitochondrial toxicants can potentially induce insulin resistance emanating from mitochondrial dysfunction. These new findings will contribute to the understanding of underlying mechanisms involved in the development of insulin resistance linked to mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

The prevalence of diabetes mellitus and diabetes-related complications is rapidly increasing worldwide, placing a substantial financial burden on healthcare systems. Approximately 537 million adults are currently diagnosed with type 1 or type 2 diabetes globally. However, interestingly, the increasing morbidity rate is primarily influenced by the effects of long-term hyperglycemia on vital organs such as the brain, the liver and the heart rather than the ability of the body to use glucose effectively. This can be attributed to the summation of the detrimental effects of excessive glucose on major vascular systems and the harmful side effects attributed to the current treatment associated with managing the disease. These drugs have been implicated in the onset and progression of cardiovascular disease, hepatocyte injury and cognitive dysfunction, thereby warranting extensive research into alternative treatment strategies. Literature has shown significant progress in utilizing metal-based compounds, specifically those containing transition metals such as zinc, magnesium and vanadium, in managing hyperglycaemia. Amongst these metals, research carried out on vanadium reflected the most promising anti-diabetic efficacy in cell culture and animal studies. This was attributed to the ability to improve glucose management in the bloodstream by enhancing its uptake and metabolism in the kidney, brain, skeletal muscle, heart and liver. Despite this, organic vanadium was considered toxic due to its accumulative characteristics. To alleviate vanadium's toxic nature while subsequently manipulating its therapeutic properties, vanadium complexes were synthesized using either vanadate or vanadyl as a base compound. This review attempts to evaluate organic vanadium salts' therapeutic and toxic effects, highlight vanadium complexes' research and provide insight into the novel dioxidovanadium complex synthesized in our laboratory to alleviate hyperglycaemia-associated macrovascular complications in the brain, heart and liver. [ABSTRACT FROM AUTHOR]

Background: Prediabetes (PD) is associated with intermediate hyperglycemia, dyslipidaemia, reduced nitric oxide (NO) bioavailability and moderate hypertension. All these factors are risk factor for preeclampsia (PE). However, the effects of the PD on placental function have not been shown. Accordingly, this study sought to investigate a possible link between maternal PD and the risk of developing PE. Methods: Pregnant female Sprague-Dawley rats (N = 18) were divided into normal, preeclamptic and prediabetic groups (n = 6 in each group) to study the effects of maternal PD on placenta function over the period of 19 days. Blood glucose and blood pressure were measured on gestational day (GND) 0, 9 and 18. Placental vascular endothelial growth factor (VEGF), placenta growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) mRNA expression were measured terminally. Data were analysed using ANOVA followed by the Tukey-Kramer post hoc test. Values of p < .05 were used to indicate statistical significance. Results: Maternal PD and PE significantly increased blood glucose, decrease NO concentration and increase in MAP by comparison to the normal pregnant control group. Maternal PD significantly decreased VEGF, PlGF mRNA expression with a slight increase in sFlt-1 mRNA expression comparison to the normal pregnant control group. Conclusions: Maternal PD is associated with placental dysfunction due to impaired glucose handling, endothelial dysfunction and an imbalance in angiogenic and antiangiogenic factors. Therefore, maternal PD is a risk factor of PE. [ABSTRACT FROM AUTHOR]

Despite the success of antidiabetic drugs in alleviation of hyperglycaemia, diabetic complications, including renal dysfunction, continue to be a burden. This raises the need to seek alternative therapies that will alleviate these complications. Accordingly, the aim of this study was to investigate the effects of dioxidovanadium(V) complex cis-[[VO.sub.2](obz)py] on renal function in diabetic rats. Streptozotocin-induced diabetic rats were treated with cis-[[VO.sub.2](obz)py] (40 mg * [kg.sup.-1]) twice every third day for five weeks. Diabetic untreated and insulin-treated rats served as the diabetic control and positive control, respectively. Blood glucose concentrations, water intake, urinary output, and mean arterial pressure (MAP) were monitored weekly for five weeks. Rats were then euthanized, and blood and kidney tissues were collected for biochemical analysis. Significant decreases in blood glucose concentrations, MAP, glomerular filtration rate (GFR), and SGLT2 expression, as well as plasma angiotensin and aldosterone concentrations, were observed in the treated groups compared with the diabetic control. The complex also increased urinary glucose concentrations, antioxidant enzymes GPx and SOD concentrations, and decreased MDA concentrations and kidney injury molecule (KIM-1) concentrations. These findings suggest that the antihyperglycaemic effects of this vanadium complex may ameliorate kidney dysfunction in diabetes. Key words: hyperglycaemia, vanadium, oxidative stress, kidney dysfunction, SGLT2, kidney injury molecule, fibrosis. En depit du succes des medicaments antidiabetiques sur l'attenuation de l'hyperglycemie, les complications du diabete, y compris le dysfonctionnement renal, continuent de constituer un fardeau. D'ou le besoin de trouver des therapies alternatives qui permettent d'attenuer ces complications. Aussi, le but de ces travaux etait-il d'etudier les effets du cis[[VO.sub.2](obz)py], un complexe de dioxydovanadium(V), sur le fonctionnement des reins chez des rats atteints de diabete. Chez des rats atteints de diabete par l'administration de streptozotocine, nous avons administre du cis-[[VO.sub.2](obz)py] a raison de 40 mg * [kg.sup.-1] a deux reprises tous les trois jours pendant cinq semaines. Nous avons utilise des rats atteints de diabete non traites ou recevant de l'insuline comme temoins diabetiques et temoins positifs, respectivement. Nous avons surveille la glycemie, l'ingestion d'eau, le debit urinaire et la tension arterielle moyenne (TAM) une fois par semaine pendant cinq semaines. Nous avons ensuite euthanasie les rats et preleve du sang et du tissu renal en vue d'epreuves biochimiques. Nous avons observe une diminution de la glycemie, de la TAM, du taux de filtration glomerulaire (TFG), de l'expression de la SGLT2, ainsi que des concentrations d'angiotensine et d'aldosterone plus marques dans les groupes de traitement que chez les temoins diabetiques. Le complexe a aussi entraine une augmentation des concentrations de glucose urinaire, d'enzymes antioxydantes GPx et SOD, et une diminution des concentrations de MDA et des concentrations de molecule 1 de lesions renales (ou KIM-1 pour << kidney injury molecule 1 >>). Ces resultats laissent entendre que les effets anti-hyperglycemiques de ce complexe de vanadium pourraient permettre d'attenuer le dysfonctionnement renal dans le diabete. [Traduit par la Redaction] Mots-cles : hyperglycemie, vanadium, stress oxydatif, dysfonctionnement renal, SGLT2, molecule de lesions renales, fibrose., Introduction Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD), which is among the leading causes of morbidity and mortality in diabetes mellitus (DM) (Yuan et al. [...]

Research has identified fetal risk factors for adult diseases, forming the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. DOHaD suggests that maternal insults during pregnancy cause structural and functional changes in fetal organs, increasing the risk of chronic diseases like type 2 diabetes mellitus (T2DM) in adulthood. It is proposed that altered maternal physiology, such as increased glucocorticoid (GC) levels associated with a dysregulated hypothalamic-pituitary-adrenal (HPA) axis in maternal stress and T2DM during pregnancy, exposes the fetus to excess GC. Prenatal glucocorticoid exposure reduces fetal growth and programs the fetal HPA axis, permanently altering its activity into adulthood. This programmed HPA axis is linked to increased risks of hypertension, cardiovascular diseases, and mental disorders in adulthood. With the global rise in T2DM, particularly among young adults of reproductive age, it is crucial to prevent its onset. T2DM is often preceded by a prediabetic state, a condition that does not show any symptoms, causing many to unknowingly progress to T2DM. Studying prediabetes is essential, as it is a reversible stage that may help prevent T2DM-related pregnancy complications. The existing literature focuses on HPA axis dysregulation in T2DM pregnancies and its link to fetal programming. However, the effects of prediabetes on HPA axis function, specifically glucocorticoid in pregnancy and fetal outcomes, are not well understood. This review consolidates research on T2DM during pregnancy, its impact on fetal programming via the HPA axis, and possible links with pregestational prediabetes. [ABSTRACT FROM AUTHOR]

Diabetics are susceptible to hepatic dysfunction risks due to hyperglycaemia and insulin therapy. Conventional diabetes treatments improve glycaemic control; however, hepatic hazards associated with these agents remains a challenge. Accordingly, this study sought to investigate the effect of a dioxidovanadium complex (V) on the hepatic function in streptozotocin-induced diabetic rats. Sprague-Dawley rats (240-250 g) were divided into 4 groups (n = 6): nondiabetic control, diabetic control, insulin-treated, and vanadium complex groups. The dioxidovanadium (10, 20, and 40 mg/kg) was administered twice every 2nd day for 5 weeks and blood glucose concentration was monitored weekly. At the end of the experimental period, all the experimental groups were sacrificed, and then the lipid profile, liver superoxide dismutase, glutathione peroxidase and malondialdehyde, plasma alanine aminotransferase and aspartate aminotransferase, and C-reactive protein (CRP) concentration were measured. The administration of dioxidovanadium significantly alleviated hyperglycaemia with concomitant attenuation in oxidative stress as evidenced by reduced malondialdehyde concentrations. Furthermore, vanadium complex abolished diabetes-induced dyslipidaemia. Lastly, vanadium complex administration attenuated the increase in alanine aminotransferase, aspartate aminotransferase, and plasma C-reactive protein. These findings suggest that this metallo-compound (dioxidovanadium) may ameliorate liver dysfunction often observed in diabetes. Key words: hyperglycaemia, oxidative stress, liver dysfunction, C-reactive protein, liver function marker enzymes. Les patients atteints de diabete sont exposes a des risques eleves de dysfonctionnement hepatique en raison de l'hyperglycemie et de l'insulinotherapie. Les traitements classiques du diabete permettent d'ameliorer la maitrise glycemique, mais les dangers hepatiques associes a ces agents demeurent un probleme. Aussi, ces travaux tentaient-ils d'etudier l'effet d'un complexe de dioxydovanadium (V) sur le fonctionnement hepatique chez le rat atteint de diabete provoque par la streptozotocine. Nous avons reparti des rats Sprague-Dawley (240-250 g) dans 4 groupes (n = 6) :(i) de temoins nondiabetiques, (ii) de temoins diabetiques, avec (iii) administration d'insuline et (iv) d'un groupe avec administration du complexe de vanadium. Nous avons administre le dioxydovanadium (10, 20 et 40 mg/kg) deux fois tous les 2e jours de 5 semaines pendant lesquelles nous avons surveille les concentrations de glucose sanguin de facon hebdomadaire. A la fin de la periode experimentale, tous les groupes experimentaux ont ete euthanasies, apres quoi nous avons evalue le profil lipidique, les taux hepatiques de superoxyde dismutase, de glutathion peroxidase et de malondialdehyde, ainsi que l'activite plasmatique de l'alanine aminotransferase et de l'aspartate aminotransferase avec les concentrations de proteine C reactive. L'administration de dioxydovanadium permettait d'attenuer l'hyperglycemie de facon notable, avec une attenuation concomitante du stress oxydatif dont temoignait une diminution des concentrations de malondialdehyde. En outre, le complexe de vanadium permettait de faire disparaitre la dyslipidemie provoquee par le diabete. Enfin, l'administration du complexe de vanadium permettait d'attenuer la hausse de l'alanine aminotransferase, de l'aspartate aminotransferase et de la proteine C reactive plasmatique. Ces resultats laissent entendre que ce compose metallique (dioxydovanadium) pourrait permettre d'attenuer le dysfonctionnement hepatique souvent observe avec le diabete. [Traduit par la Redaction] Mots-cles : hyperglycemie, stress oxydatif, dysfonctionnement hepatique, proteine C reactive, marqueurs enzymatiques du fonctionnement hepatique., Introduction Liver dysfunction has been reported in diabetes mellitus and is associated with oxidative stress and low-grade inflammation (Amos et al. 1997). Hepatic oxidative stress is often marked with increases [...]

Maternal type 2 diabetes mellitus (T2DM) has been shown to result in foetal programming of the hypothalamic–pituitary–adrenal (HPA) axis, leading to adverse foetal outcomes. T2DM is preceded by prediabetes and shares similar pathophysiological complications. However, no studies have investigated the effects of maternal prediabetes on foetal HPA axis function and postnatal offspring development. Hence, this study investigated the effects of pregestational prediabetes on maternal HPA axis function and postnatal offspring development. Pre-diabetic (PD) and non-pre-diabetic (NPD) female Sprague Dawley rats were mated with non-prediabetic males. After gestation, male pups born from the PD and NPD groups were collected. Markers of HPA axis function, adrenocorticotropin hormone (ACTH) and corticosterone, were measured in all dams and pups. Glucose tolerance, insulin and gene expressions of mineralocorticoid (MR) and glucocorticoid (GR) receptors were further measured in all pups at birth and their developmental milestones. The results demonstrated increased basal concentrations of ACTH and corticosterone in the dams from the PD group by comparison to NPD. Furthermore, the results show an increase basal ACTH and corticosterone concentrations, disturbed MR and GR gene expression, glucose intolerance and insulin resistance assessed via the Homeostasis Model Assessment (HOMA) indices in the pups born from the PD group compared to NPD group at all developmental milestones. These observations reveal that pregestational prediabetes is associated with maternal dysregulation of the HPA axis, impacting offspring HPA axis development along with impaired glucose handling. [ABSTRACT FROM AUTHOR]