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Цукровий діабет є одним з найпоширеніших незаразних захворювань котів та собак і на сучасному етапі набуває епідемічних масштабів. Метою досліджень було встановлення активності ферментів, що є маркерами функціональної активності печінки: аланінамінотрансферази, аспарагін-амінотрансферази, лужної фосфатази та сорбітолдегідрогенази у котів з цукровим діабетом та дослідження динаміки активності сорбітолдегідрогенази. Для досліджень було сформовано дві групи котів віком 5–7 років (самці та самки) по 10 голів у кожній. Контрольна група складалась із клінічно здорових тварин, дослідна – із тварин, що мали діагноз цукровий діабет. Результати досліджень показали, що у котів дослідної групи вміст глюкози був у 3,31 раза вищим, ніж у контрольній групі. Фруктозамін характеризує тривалість гіперглікемії, і у котів з цукровим діабетом його вміст перевищував контрольні показники на 32 %, що є ознакою тривалого підвищення вмісту глюкози. У результаті цукрового діабету порушується водно-сольовий обмін, зокрема зростає осмоляльність крові. Визначення активності ферментів показало, що активність трансаміназ зросла вдвічі, тоді як активність ЛФ зростала на 25 %. Концентрація загального білірубіну зростала порівняно до контролю більш, ніж на третину. Активність СДГ у котів з цукровим діабетом була у 2,25 вищою, ніж у тварин контрольної групи. Активність даного ферменту, на відміну від активності трансаміназ, зростає у перші доби після симптомів печінкової дисфункції. Установлено, що у котів з цукровим діабетом розвивається порушення функцій печінки, що проявляється у зміні активності аланінамінотрансферази, аспарагінамінотрансферази, лужної фосфатази, збільшення концентрації білірубіну та збільшення активності сорбітолдегідрогенази. Даний фермент є цінним біохімічним маркером порушень функції печінки на ранніх стадіях розвитку патології., Diabetes mellitus is one of the most widely spread non-infectious cats and dogs diseases and in modern times it is reaching epidemic levels. The purpose of the research was to determine enzymes activity, which is a marker of liver’s functional activity: alanine aminotransferase, asparagine aminotransferase, alkaline phosphatase and sorbitol dehydrogenase in cats suffering from diabetes mellitus, and another purpose was to study the dynamics of sorbitol dehydrogenase activity. Two groups of cats aged 5–7 years old (males and females) 10 cats in each group were formed for the research. A control group comprised clinically healthy animals, experimental group comprised animals diagnosed with diabetes mellitus. The results of the research showed that in cats of the experimental group the glucose content was 3.31 times as high as in cats of a control group. Fructosamine characterizes the duration of hyperglycemia and in cats diagnosed with diabetes mellitus its content overshot the control indices by 32 %, that testifies to a long-standing increase in glucose amount. Because of diabetes mellitus, water-salt metabolism is damaged, for instance blood osmolality is increased. The determination of enzymes activity showed that transaminase activity doubled, whereas the alkaline phosphatase activity increased by 25 %. The concentration of total bilirubin increased more than three-fold as compared to the control. The sorbitol dehydrogenase activity in cats diagnosed with diabetes mellitus was in 2.25 times higher as compared to the animals in a control group. The activity of this enzyme, contrary to transaminase activity, is increased during the first days after hepatic dysfunction symptoms. Thus, in cats diagnosed with diabetes mellitus, liver function abnormality is developed which is manifested in activity changes of alanine aminotransferase, asparagine aminotransferase, alkaline phosphatase in the increase in bilirubin concentration as well as in the increase of sorbitol deh, Сахарный диабет является одним из самых распространенных незаразных заболеваний кошек и собак и на современном этапе приобретает эпидемических масштабов. Целью исследований было установление активности ферментов, которые являются маркерами функциональной активности печени аланинаминотрансферазы, аспарагин-аминотрансферазы, щелочные фосфатазы и сорбитолдегидрогеназы у котов с сахарным диабетом и исследования динамики активности сорбитолдегидрогеназы. Для исследований были сформированы две группы кошек возрастом 5-7 лет (самцы и самки) по 10 голов в каждой. Контрольная группа состояла из клинически здоровых животных, исследовательская - из животных, имевших диагноз сахарный диабет. Результаты исследований показали, что у котов исследовательской группы содержание глюкозы был в 3,31 раза выше, чем в контрольной группе. Фруктозамин характеризует продолжительность гипергликемии, и у котов с сахарным диабетом его содержание превышало контрольные показатели на 32%, что является признаком длительного повышения содержания глюкозы. В результате сахарного диабета нарушается водно-солевой обмен, в частности растет осмоляльность крови. Определение активности ферментов показало, что активность трансаминаз выросла вдвое, тогда как активность ЛФ росла на 25%. Концентрация общего билирубина росла по сравнению с контролем более чем на треть. Активность СДГ у котов с сахарным диабетом была в 2,25 выше, чем у животных контрольной группы. Активность данного фермента, в отличие от активности трансаминаз, растет в первые сутки после симптомов печеночной дисфункции. Установлено, что у котов с сахарным диабетом развивается нарушение функции печени, что проявляется в изменении активности печеночных, аспарагинаминотрансферазы, щелочной фосфатазы, увеличении концентрации билирубина и повышении активности сорбитолдегидрогеназы. Данный фермент является ценным биохимическим маркером нарушений функции печени на ранних стадиях развития патологии.

Disrupted endothelial metabolism is linked to endothelial dysfunction and cardiovascular disease. Targeted metabolic inhibitors are potential therapeutics; however, their systemic impact on endothelial metabolism remains unknown. In this study, we combined stable isotope labeling with 13C metabolic flux analysis (13C MFA) to determine how targeted inhibition of the polyol (fidarestat), pentose phosphate (DHEA), and hexosamine biosynthetic (azaserine) pathways alters endothelial metabolism. Glucose, glutamine, and a four-carbon input to the malate shuttle were important carbon sources in the baseline human umbilical vein endothelial cell (HUVEC) 13C MFA model. We observed two to three times higher glutamine uptake in fidarestat and azaserine-treated cells. Fidarestat and DHEA-treated HUVEC showed decreased 13C enrichment of glycolytic and TCA metabolites and amino acids. Azaserine-treated HUVEC primarily showed 13C enrichment differences in UDP-GlcNAc. 13C MFA estimated decreased pentose phosphate pathway flux and increased TCA activity with reversed malate shuttle direction in fidarestat and DHEA-treated HUVEC. In contrast, 13C MFA estimated increases in both pentose phosphate pathway and TCA activity in azaserine-treated cells. These data show the potential importance of endothelial malate shuttle activity and suggest that inhibiting glycolytic side branch pathways can change the metabolic network, highlighting the need to study systemic metabolic therapeutic effects.

Disrupted endothelial metabolism is linked to endothelial dysfunction and cardiovascular disease. Targeted metabolic inhibitors are potential therapeutics; however, their systemic impact on endothelial metabolism remains unknown. In this study, we combined stable isotope labeling with 13C metabolic flux analysis (13C MFA) to determine how targeted inhibition of the polyol (fidarestat), pentose phosphate (DHEA), and hexosamine biosynthetic (azaserine) pathways alters endothelial metabolism. Glucose, glutamine, and a four-carbon input to the malate shuttle were important carbon sources in the baseline human umbilical vein endothelial cell (HUVEC) 13C MFA model. We observed two to three times higher glutamine uptake in fidarestat and azaserine-treated cells. Fidarestat and DHEA-treated HUVEC showed decreased 13C enrichment of glycolytic and TCA metabolites and amino acids. Azaserine-treated HUVEC primarily showed 13C enrichment differences in UDP-GlcNAc. 13C MFA estimated decreased pentose phosphate pathway flux and increased TCA activity with reversed malate shuttle direction in fidarestat and DHEA-treated HUVEC. In contrast, 13C MFA estimated increases in both pentose phosphate pathway and TCA activity in azaserine-treated cells. These data show the potential importance of endothelial malate shuttle activity and suggest that inhibiting glycolytic side branch pathways can change the metabolic network, highlighting the need to study systemic metabolic therapeutic effects.

Disrupted endothelial metabolism is linked to endothelial dysfunction and cardiovascular disease. Targeted metabolic inhibitors are potential therapeutics; however, their systemic impact on endothelial metabolism remains unknown. In this study, we combined stable isotope labeling with 13C metabolic flux analysis (13C MFA) to determine how targeted inhibition of the polyol (fidarestat), pentose phosphate (DHEA), and hexosamine biosynthetic (azaserine) pathways alters endothelial metabolism. Glucose, glutamine, and a four-carbon input to the malate shuttle were important carbon sources in the baseline human umbilical vein endothelial cell (HUVEC) 13C MFA model. We observed two to three times higher glutamine uptake in fidarestat and azaserine-treated cells. Fidarestat and DHEA-treated HUVEC showed decreased 13C enrichment of glycolytic and TCA metabolites and amino acids. Azaserine-treated HUVEC primarily showed 13C enrichment differences in UDP-GlcNAc. 13C MFA estimated decreased pentose phosphate pathway flux and increased TCA activity with reversed malate shuttle direction in fidarestat and DHEA-treated HUVEC. In contrast, 13C MFA estimated increases in both pentose phosphate pathway and TCA activity in azaserine-treated cells. These data show the potential importance of endothelial malate shuttle activity and suggest that inhibiting glycolytic side branch pathways can change the metabolic network, highlighting the need to study systemic metabolic therapeutic effects.

Erythritol is the preferential carbon source for most brucellae, a group of facultative intracellular bacteria that cause a worldwide zoonosis. Since this polyol is abundant in genital organs of ruminants and swine, it is widely accepted that erythritol accounts at least in part for the characteristic genital tropism of brucellae. Nevertheless, proof of erythritol availability and essentiality during Brucella intracellular multiplication has remained elusive. To investigate this relationship, we compared ΔeryH (erythritol-sensitive and thus predicted to be attenuated if erythritol is present), ΔeryA (erythritol-tolerant but showing reduced growth if erythritol is a crucial nutrient) and wild type B. abortus in various infection models. This reporting system indicated that erythritol was available but not required for B. abortus multiplication in bovine trophoblasts. However, mice and humans have been considered to lack erythritol, and we found that it was available but not required for B. abortus multiplication in human and murine trophoblastic and macrophage-like cells, and in mouse spleen and conceptus (fetus, placenta and envelopes). Using this animal model, we found that B. abortus infected cells and tissues contained aldose reductase, an enzyme that can account for the production of erythritol from pentose cycle precursors., SCOPUS: ar.j, info:eu-repo/semantics/published

With increasing prevalence of diabetes and its associated complications is a priority of health service globally. Diabetic ocular complications are most common in both type-1 and type-2 diabetes, considering the fifth most common cause of legal blindness. According to WHO, cataract is 33% of all type of visual impairment. Simply diabetic cataracts are characterized by cortical or posterior subcapsular opacities. Aldose reductase and polyol are responsible for diabetes ocular complications. Intracellular accumulation of sorbitol leads to osmotic stress resulting in the formation of lens opacities. Several clinical studies investigated the role of phacoemulsification surgery and its post surgery complications. Researcher are trying to develop aldose reductase inhibitors and antioxidents, may be effective treatment to prevent or cure diabetes cataract.

With increasing prevalence of diabetes and its associated complications is a priority of health service globally. Diabetic ocular complications are most common in both type-1 and type-2 diabetes, considering the fifth most common cause of legal blindness. According to WHO, cataract is 33% of all type of visual impairment. Simply diabetic cataracts are characterized by cortical or posterior subcapsular opacities. Aldose reductase and polyol are responsible for diabetes ocular complications. Intracellular accumulation of sorbitol leads to osmotic stress resulting in the formation of lens opacities. Several clinical studies investigated the role of phacoemulsification surgery and its post surgery complications. Researcher are trying to develop aldose reductase inhibitors and antioxidents, may be effective treatment to prevent or cure diabetes cataract.

With increasing prevalence of diabetes and its associated complications is a priority of health service globally. Diabetic ocular complications are most common in both type-1 and type-2 diabetes, considering the fifth most common cause of legal blindness. According to WHO, cataract is 33% of all type of visual impairment. Simply diabetic cataracts are characterized by cortical or posterior subcapsular opacities. Aldose reductase and polyol are responsible for diabetes ocular complications. Intracellular accumulation of sorbitol leads to osmotic stress resulting in the formation of lens opacities. Several clinical studies investigated the role of phacoemulsification surgery and its post surgery complications. Researcher are trying to develop aldose reductase inhibitors and antioxidents, may be effective treatment to prevent or cure diabetes cataract.

Objectives: Although intensive therapy for type 2 diabetes (T2D) prevents microvascular complications, 10% of well-controlled T2D patients develop microangiopathy. Therefore, the identification of risk markers for microvascular complications in well-controlled T2D patients is important. Recent studies have demonstrated that high-dose glucose induces neutrophil extracellular trap (NET) formation, which can be a risk for microvascular disorders. Thus, we attempted to determine the correlation of circulating NET levels with clinical/laboratory parameters in well-controlled T2D patients and to reveal the mechanism of NET formation induced by high-dose glucose. Methods: Circulating NET levels represented by myeloperoxidase (MPO)-DNA complexes in the serum of 11 well-controlled T2D patients and 13 healthy volunteers were determined by enzyme-linked immunosorbent assay. The pathway involved in the NET formation induced by high-dose glucose was determined using specific inhibitors. Results: Serum MPO-DNA complex levels were significantly higher in some well-controlled T2D patients in correlation with the clinical/laboratory parameters which have been regarded as risk markers for microvascular complications. The aldose reductase inhibitor, ranirestat, could inhibit the NET formation induced by high-dose glucose. Conclusions: Elevated levels of circulating NETs can be a risk marker for microvascular complications in well-controlled T2D patients. The polyol pathway is involved in the NET formation induced by high-dose glucose.

Objectives: Although intensive therapy for type 2 diabetes (T2D) prevents microvascular complications, 10% of well-controlled T2D patients develop microangiopathy. Therefore, the identification of risk markers for microvascular complications in well-controlled T2D patients is important. Recent studies have demonstrated that high-dose glucose induces neutrophil extracellular trap (NET) formation, which can be a risk for microvascular disorders. Thus, we attempted to determine the correlation of circulating NET levels with clinical/laboratory parameters in well-controlled T2D patients and to reveal the mechanism of NET formation induced by high-dose glucose. Methods: Circulating NET levels represented by myeloperoxidase (MPO)-DNA complexes in the serum of 11 well-controlled T2D patients and 13 healthy volunteers were determined by enzyme-linked immunosorbent assay. The pathway involved in the NET formation induced by high-dose glucose was determined using specific inhibitors. Results: Serum MPO-DNA complex levels were significantly higher in some well-controlled T2D patients in correlation with the clinical/laboratory parameters which have been regarded as risk markers for microvascular complications. The aldose reductase inhibitor, ranirestat, could inhibit the NET formation induced by high-dose glucose. Conclusions: Elevated levels of circulating NETs can be a risk marker for microvascular complications in well-controlled T2D patients. The polyol pathway is involved in the NET formation induced by high-dose glucose.

高血糖は糖尿病合併症の発症と密接に関与している.しかし,グルコースは重 要なエネルギー源であり生命維持に不可欠である.それにもかかわらず,糖尿病患者にとって 過剰なグルコースの存在は致命傷になってしまう.グルコースはそれほど毒性の高い化合物な のだろうか.多くの人は疑問を抱くに違いない.我々の生体内では,グルコースは2種の異性 体(α-and β-anomers)をもった環状体(ring fo㎜)として存在する.この異性体の変換時に一過 性にアルデヒド中間体(open-chain,free aldehyde form)が生成される.このアルデヒド中間体 は脱水素酵素により安定な酸へ(グルコン酸経路),還元酵素によりアルコールへと代謝される (ポリオール経路).グルコースによる組織障害はこのアルデヒドによる直接反応またその代謝 系を介して誘起される.言い換えれば,アルデヒド毒性である.

高血糖は糖尿病合併症の発症と密接に関与している.しかし,グルコースは重 要なエネルギー源であり生命維持に不可欠である.それにもかかわらず,糖尿病患者にとって 過剰なグルコースの存在は致命傷になってしまう.グルコースはそれほど毒性の高い化合物な のだろうか.多くの人は疑問を抱くに違いない.我々の生体内では,グルコースは2種の異性 体(α-and β-anomers)をもった環状体(ring fo㎜)として存在する.この異性体の変換時に一過 性にアルデヒド中間体(open-chain,free aldehyde form)が生成される.このアルデヒド中間体 は脱水素酵素により安定な酸へ(グルコン酸経路),還元酵素によりアルコールへと代謝される (ポリオール経路).グルコースによる組織障害はこのアルデヒドによる直接反応またその代謝 系を介して誘起される.言い換えれば,アルデヒド毒性である.

Diabetes-induced renal complications, i.e. diabetes nephropathy, are a major cause of morbidity and mortality. The exact mechanism mediating the negative influence of hyperglycaemia on renal function is unclear, although several hypotheses have been postulated. Glucose-induced excessive formation of reactive oxygen species (ROS) and increased glucose flux through the polyol pathway are two major mechanisms that have recently gained increasing support. In order to investigate the development of hyperglycaemia-induced renal alterations further, it is of great importance to use an animal model in agreement with the pathological development in diabetic patients. The aims of these investigations were to evaluate the streptozotocin (STZ)-diabetic Wistar Furth rat as a model for human diabetic nephropathy and to investigate involvement of ROS and the polyol pathway in development of diabetes-induced renal alterations. The used STZ-diabetic animal model displayed several similarities with the progression of human disease, including initial hyperfiltration and albuminuria. However, the observed proteinuria could be partly linked to the STZ treatment per se, making the use of this animal model less suitable for research concerning diabetes-induced urinary protein leakage. The diabetic state induced numerous alterations in renal function and metabolism, including increased oxygen consumption, decreased renal oxygen tension (pO2), and altered lactate/pyruvate ratio. These renal alterations were preventable by daily treatment with either a radical scavenger (α-tocopherol) or an aldose reductase inhibitor (AL-1576). In separate experiments the influence of nitric oxide (NO) on renal blood perfusion and pO2 was investigated. The diabetic animals displayed a larger increase in renal NO activity after injecting the NO substrate L-arginine compared to non-diabetic animals, suggesting substrate limitation of the nitric oxide synthase during chronic hyperglycaemia. In conclusion, the r

Diabetes-induced renal complications, i.e. diabetes nephropathy, are a major cause of morbidity and mortality. The exact mechanism mediating the negative influence of hyperglycaemia on renal function is unclear, although several hypotheses have been postulated. Glucose-induced excessive formation of reactive oxygen species (ROS) and increased glucose flux through the polyol pathway are two major mechanisms that have recently gained increasing support. In order to investigate the development of hyperglycaemia-induced renal alterations further, it is of great importance to use an animal model in agreement with the pathological development in diabetic patients. The aims of these investigations were to evaluate the streptozotocin (STZ)-diabetic Wistar Furth rat as a model for human diabetic nephropathy and to investigate involvement of ROS and the polyol pathway in development of diabetes-induced renal alterations. The used STZ-diabetic animal model displayed several similarities with the progression of human disease, including initial hyperfiltration and albuminuria. However, the observed proteinuria could be partly linked to the STZ treatment per se, making the use of this animal model less suitable for research concerning diabetes-induced urinary protein leakage. The diabetic state induced numerous alterations in renal function and metabolism, including increased oxygen consumption, decreased renal oxygen tension (pO2), and altered lactate/pyruvate ratio. These renal alterations were preventable by daily treatment with either a radical scavenger (α-tocopherol) or an aldose reductase inhibitor (AL-1576). In separate experiments the influence of nitric oxide (NO) on renal blood perfusion and pO2 was investigated. The diabetic animals displayed a larger increase in renal NO activity after injecting the NO substrate L-arginine compared to non-diabetic animals, suggesting substrate limitation of the nitric oxide synthase during chronic hyperglycaemia. In conclusion, the r