Role of thiamine status and genetic variability in transketolase and other pentose phosphate cycle enzymes in the progression of diabetic nephropathy

Pácal, Lukáš; Tomandl, Josef; Svojanovský, Jan; Krusová, Darja; Štěpánková, Soňa; Řehořová, Jitka; Olšovský, Jindřich; Bělobrádková, Jana; Tanhäuserová, Veronika; Tomandlová, Marie; Mužı́k, Jan; Kaňková, Kateřina

doi:10.1093/ndt/gfq550

Cited by 42 publications

(37 citation statements)

References 14 publications

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“…However, a further study has shown increased plasma thiamine levels with progressive renal impairment and proteinuria suggesting decreased renal clearance of thiamine (21)…”

Section: Mechanismsmentioning

confidence: 99%

Thiamine deficiency in diabetes mellitus and the impact of thiamine replacement on glucose metabolism and vascular disease

Page

Laight

Cummings

2011

International Journal of Clinical Practice

115

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Summary Despite the targeting of traditional risk factors for cardiovascular disease, disease burden has not been completely eliminated. Thiamine is an essential cofactor in carbohydrate metabolism and individuals with diabetes are thiamine deficient. The pathophysiology of recognised complications of thiamine deficiency is similar to that underlying atherosclerosis and the metabolic syndrome, namely oxidative stress, inflammation and endothelial dysfunction. This review examines the mechanisms by which thiamine deficiency occurs in individuals with diabetes, how this deficiency leads to hyperglycaemic‐induced damage, and the effect of thiamine replacement on vascular disease, endothelial function and oxidative stress. Thiamine administration can prevent the formation of harmful by‐products of glucose metabolism, reduce oxidative stress and improve endothelial function. The potential benefit of long‐term replacement in those with diabetes is not yet known but may reduce cardiovascular risk and angiopathic complications.

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“…However, a further study has shown increased plasma thiamine levels with progressive renal impairment and proteinuria suggesting decreased renal clearance of thiamine (21)…”

Section: Mechanismsmentioning

confidence: 99%

Thiamine deficiency in diabetes mellitus and the impact of thiamine replacement on glucose metabolism and vascular disease

Page

Laight

Cummings

2011

International Journal of Clinical Practice

115

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“…7 Thiamine is the co-factor of transketolase in pentose phosphate pathway and in high doses it increases the activity of this enzyme leading to disposal of excess cytosolic glucose. 16 The products of pentose phosphate pathway are non-harmful to cell. On the other hand the decreased flux through hexosamine and protein kinase C pathway decreases glycosylation of glucose transporters.…”

Section: Discussionmentioning

confidence: 99%

A comparative study of thiamine with metformin on fasting blood glucose of diabetic albino rats

Choudhury

Loc

Debbarma

et al. 2016

Int J Basic Clin Pharmacol

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INTRODUCTIONDiabetes mellitus refers to a group of common metabolic disorders that share the phenotype of hyperglycaemia. Various distinct types of DM are caused by a complex interaction of genetics and environmental factors. Depending on the aetiology of DM factors contributing to hyperglycaemia include reduced insulin secretion, decreased glucose utilization, and increased glucose production. When fully expressed diabetes is characterized by fasting hyperglycaemia. The effects of diabetes mellitus include long term damage, dysfunction and failure of various organs especially heart, kidneys, eyes and blood vessels. Diabetes may present with characteristic symptoms such as thirst, polyurea, blurring of vision, polyphagia, and weight loss and in its most severe form diabetic ketoacidosis and non ketotic hyperosmolar state, which in absence of effective intervention lead to stupor, coma and death. At present, India is considered as the diabetic capital of the world by WHO. There are approximately 3.5 crore diabetics in India, and this figure is expected to increase up to 5.2 crore by 2025. Every fifth patient visiting a consulting physician is a diabetic. By the year 2025 it is predicted that India will have a rise of 59 percent of diabetics in the population -which is the highest number of diabetic patients in the world. 2 ABSTRACTBackground: Thiamine is a member of the vitamin B family. Thiamine is necessary for normal insulin synthesis and secretion. In diabetes thiamine and its derivative benfotiamine showed promising results in prevention of microvascular complications. Some experimental and clinical studies have shown the antihyperglycaemic effect of thiamine. This study compared the antihyperglycaemic effect of thiamine with metformin in streptozotocinnicotinamide induced diabetic albino rats. Methods: 24 albino rats were taken and divided into four groups of six rats in each group. The groups were normal control, diabetic control, diabetic rats treated with thiamine, diabetic rats treated with metformin. Diabetes was induced in three groups by intraperitoneal injection of Streptozotocin in the dose of 60 mg/kg. To have an ideal type 2 diabetes model nicotinamide was administered 120 mg/ kg intraperitoneally fifteen minutes before streptozotocin administration. After successful induction of diabetes thiamine and metformin were given to the respective group for a period of 6 weeks. Fasting blood glucose was estimated on day 0, 7, 14, 21, 28, 35, 42 of treatment. Results: In this study both thiamine and metformin showed significant antihyperglycaemic effect (p<0.05). Further studies are needed to evaluate and compare the antihyperglycaemic effect of thiamine with other established anti diabetic drugs. Conclusions: From this study we concluded that individually both thiamine and metformin were effective in controlling hyperglycaemia but metformin was better in achieving normal mean FBS. Further studies are required to validate the antihyperglycaemic effect of thiamine. Study taking different doses of thiamine ...

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“…TKT activity was measured indirectly as previously described [26] using kinetic NADPH-dependent method utilizing triose phosphate isomerase (180 U ml −1 ) and glycerol-3-phosphate dehydrogenase (7.3 U ml −1 ). Reaction rates were expressed as picomoles of substrate converted per second under specified conditions related to milligrams of haemoglobin in erythrocyte lysate.…”

Section: Tkt Activity and Thiamine Effectmentioning

confidence: 99%

Dysfunctional protection against advanced glycation due to thiamine metabolism abnormalities in gestational diabetes

et al. 2016

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While the pathogenic role of dicarbonyl stress and accelerated formation of advanced glycation end products (AGEs) to glucose intolerance and to the development of diabetic complications is well established, little is known about these processes in gestational diabetes mellitus (GDM), a condition pathogenically quite similar to type 2 diabetes. The aims of the present study were (i) to determine plasma thiamine and erythrocyte thiamine diphosphate (TDP) and transketolase (TKT) activity in pregnant women with and without GDM, (ii) to assess relationships between thiamine metabolism parameters and selected clinical, biochemical and anthropometric characteristics and, finally, (iii) to analyse relationship between variability in the genes involved in the regulation of transmembrane thiamine transport (i.e. SLC19A2 and SLC19A3) and relevant parameters of thiamine metabolism. We found significantly lower plasma BMI adjusted thiamine in women with GDM (P = 0.002, Mann-Whitney) while levels of erythrocyte TDP (an active TKT cofactor) in mid-trimester were significantly higher in GDM compared to controls (P = 0.04, Mann-Whitney). However, mid-gestational TKT activity - reflecting pentose phosphate pathway activity - did not differ between the two groups (P > 0.05, Mann-Whitney). Furthermore, we ascertained significant associations of postpartum TKT activity with SNPs SLC19A2 rs6656822 and SLC19A3 rs7567984 (P = 0.03 and P = 0.007, resp., Kruskal-Wallis). Our findings of increased thiamine delivery to the cells without concomitant increase of TKT activity in women with GDM therefore indicate possible pathogenic role of thiamine mishandling in GDM. Further studies are needed to determine its contribution to maternal and/or neonatal morbidity.

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Role of thiamine status and genetic variability in transketolase and other pentose phosphate cycle enzymes in the progression of diabetic nephropathy

Abstract: The results support the role of 'functional' thiamine deficiency in the development of hyperglycaemia-related pathology. Limited intracellular availability of active TKT co-factor seems to be a dominant abnormality.

Cited by 42 publications

References 14 publications

Thiamine deficiency in diabetes mellitus and the impact of thiamine replacement on glucose metabolism and vascular disease

Thiamine deficiency in diabetes mellitus and the impact of thiamine replacement on glucose metabolism and vascular disease

A comparative study of thiamine with metformin on fasting blood glucose of diabetic albino rats

Dysfunctional protection against advanced glycation due to thiamine metabolism abnormalities in gestational diabetes

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