The effect of high glucose on polyol pathway activity and myoinositol metabolism in cultured human endothelial cells

Hawthorne, Gillian; Bartlett, K.; Hetherington, C.; Alberti, K. G. M. M.

doi:10.1007/bf00265088

Cited by 46 publications

(22 citation statements)

References 19 publications

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“…Contributory mechanisms include increased oxidative stress as a result of increased generation of free radicals due to hyperglycaemia [41]. Furthermore, hyperglycaemia induces protein kinase C activation and depletion of essential nitric oxide synthase cofactors resulting in deactivation of nitric oxide and nitric oxide synthase, thereby reducing nitric oxide bioavailability [42,43]. Hyperglycaemia has also recently been shown to enhance expression of endothelin-1, a vasoconstrictor that antagonizes the effects of nitric oxide [44].…”

Section: Discussionmentioning

confidence: 99%

Endothelium-dependent and independent vasodilation studied at normoglycaemia in Type I diabetes mellitus with and without microalbuminuria

et al. 2001

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Aims/hypothesis. We examined whether endothelial function is impaired in patients with Type I (insulindependent) diabetes mellitus under conditions of near-normoglycaemia compared with age-matched healthy control subjects. Our aim was to determine whether microalbuminuria is associated with endothelial dysfunction in Type I diabetes. Methods. Endothelial function, measured as postischaemic flow-mediated dilatation of the brachial artery using ultrasound, was compared among 17 microalbuminuric and 17 normoalbuminuric diabetic patients, and 17 control subjects. Glyceryl trinitratemediated dilatation of the brachial artery was used to measure endothelium-independent function. All diabetic patients were studied at near-normoglycaemia, using insulin and 5 % dextrose infusions to maintain blood glucose between 3.5 and 8.0 mmol/l. Results. Flow-mediated dilatation was significantly lower in microalbuminuric diabetic patients (3.2 0.3 %) compared with normoalbuminuric diabetic patients (5.4 0.6 %) and control subjects (7.9 0.6 %, p < 0.001). Normoalbuminuric diabetic patients also had significantly lower flow-mediated dilatation than control subjects (p = 0.01). Glyceryl trinitrate mediated dilatation was significantly lower in the microalbuminuric patients compared with the control subjects (11.9 1.1 % vs 20.0 1.2 %, p = 0.001). Albumin excretion rate and glycated haemoglobin showed a significant negative independent correlation with flow-mediated dilatation (both p < 0.05). Conclusion/interpretation. Type I diabetic patients show endothelial dysfunction at near-normoglycaemia compared with the control subjects, and this abnormality is more marked in diabetic patients with microalbuminuria. Endothelial dysfunction in Type I diabetes is related to the albumin excretion rate and glycaemic control. The presence of endothelial dysfunction in normoalbuminuric diabetic patients suggests it could precede microalbuminuria as an early risk marker for cardiovascular disease. [Diabetologia (2001) 44: 593±601]

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Section: Discussionmentioning

confidence: 99%

Endothelium-dependent and independent vasodilation studied at normoglycaemia in Type I diabetes mellitus with and without microalbuminuria

et al. 2001

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“…A relatively constant amount enters the pentose phosphate shunt [6] while, in the presence of supraphysiological concentrations, aldose reductase may activate the polyol pathway [16,17]. Thiamine reduces anaerobic glycolysis and increases the aerobic pentose phosphate pathway by helping transketolase to transform glyceraldehyde-P into ribulose-P [6].…”

Section: Discussionmentioning

confidence: 99%

Thiamine corrects delayed replication and decreases production of lactate and advanced glycation end-products in bovine retinal and human umbilical vein endothelial cells cultured under high glucose conditions

et al. 1996

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High glucose concentrations impair the replication of cultured human umbilical vein (HUVEC) [1][2][3] and bovine retinal endothelial cells (BREC) [4] and this may be secondary to enhanced glycolytic flux. Altered concentrations of intermediate phosphorylated metabolites could play a role in determining cell damage. In particular, increased availability of glyceraldehyde 3-phosphate (G3P), which is much more active than glucose in promoting protein glycation and AGE formation [5], might be one of the mechanism(s) involved.Thiamine (vitamin B 1 ) acts as a coenzyme for transketolase [6], pyruvate-dehydrogenase [7] and a -ketoglutarate-dehydrogenase [8]. The former shifts G3P from glycolysis to the pentose phosphate shunt, the second transforms pyruvate in acetyl-coenzyme A, which then enters the Krebs cycle, and the third catalyses the oxidation of ketoglutaric acid to succinyl-CoA within the Krebs cycle.The aim of this study was to ascertain whether thiamine would modify glycolysis, AGE production and replication in HUVEC and BREC cultured in high glucose concentrations. Diabetologia (1996) Summary This study aimed at verifying whether thiamine, a co-enzyme which decreases intracellular glycolysis metabolites by allowing pyruvate and glyceraldheyde 3-phosphate to enter the Krebs cycle and the pentose-phosphate shunt, respectively, corrects delayed replication caused by high glucose concentrations in cultured human umbilical vein (HU-VEC) and bovine retinal endothelial cells (BREC). After incubation in physiological (5.6 mmol/l) or high (28.0 mmol/l) glucose with or without 150 m mol/l thiamine, cells were counted and proliferation assessed by mitochondrial dehydrogenase activity. Lactate was measured in both cell types as an index of glycolytic activity and fluorescent advanced glycosylation end-products (AGE) concentration was determined in the HUVEC lysate. Both cell counts and proliferation assays in either of the cell types confirmed the impairment to cell replication induced by high glucose. When thiamine was added to cells kept under high glucose conditions, the number of surviving cells was significantly increased and the reduced cell proliferation appeared to be corrected. Lactate assays confirmed the increased production of this metabolite by BREC and HUVEC in high glucose, which was reduced by thiamine. Fluorescent AGE determination showed that thiamine may prevent non-enzymatic glycation in HUVEC. Thiamine restores cell replication, decreases the glycolytic flux and prevents fluorescent AGE formation in endothelial cells cultured in high glucose, suggesting that abnormal levels of glycolytic metabolite(s) may damage cells.

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“…Chronic hyperglycaemia increases aldose reductase activity leading to an increase in glucose metabolism through the polyol pathway [109,110] in which it is first metabolised to sorbitol and subsequently to fructose (Fig. 3).…”

Section: Aldose Reductase and The Polyol Pathwaymentioning

confidence: 99%

“…Aldose reductase has been shown to be present in the vascular endothelial cells [111] and is the rate-limiting enzyme in the initial conversion of glucose to sorbitol. This process is dependent on nicotinamide-adenine dinucleotide phosphate (NADPH) and therefore results in an increase in its use [109,112]. Because NADPH is also an essential cofactor for NOS for the synthesis of NO, its depletion as a result of chronic hyperglycaemia could lead to a reduction in NO production.…”

Section: Aldose Reductase and The Polyol Pathwaymentioning

confidence: 99%

Nitric oxide and vascular responses in Type I diabetes

2000

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Diabetic microangiopathy and macroangiopathy are the principal causes of morbidity and mortality in patients with diabetes mellitus [1±3]. Patients with Type I (insulin-dependent) diabetes mellitus have a three to sixfold increased risk of cardiovascular death before the age of 60 compared with non-diabetic subjects [4]. Established risk factors for coronary heart disease (CHD) do not, however, fully explain the increased risk in Type I diabetic patients [5].The vascular endothelium has a key role in maintaining homeostasis of the vasculature through the synthesis of vasoactive substances that modulate vascular tone, inhibit platelet aggregation and vascular smooth muscle cell (VSMC) proliferation [6, 7]. Endothelial dysfunction has been suggested to be an early event in diabetic vascular disease [8, 9]. The discovery of endothelium-derived nitric oxide (NO) in the late 1980 s [10] has considerably improved our understanding in vascular biology and pathogenesis of endothelial dysfunction. With the use of techniques such as brachial artery ultrasonography, venous occlusion plethysmography and brachial artery infusion of endothelium-dependent vasoactive agents, endothelial function can be indirectly assessed in different vascular beds. Most published reviews have focused on Type II (non-insulin-dependent) diabetes mellitus rather than Type I diabetes. We reviewed the current evidence for endothelium-mediated vascular dysfunction in Type I diabetes following an extensive literature search from both Medline and PubMed (1965±1999) using the following keywords:`Type I diabetes mellitus',`endothelial function',`nitric oxide', vasodilatation'. Potential mechanisms which could be involved in endothelial dysfunction in Type I diabetes are discussed. Diabetologia (2000)

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The effect of high glucose on polyol pathway activity and myoinositol metabolism in cultured human endothelial cells

Cited by 46 publications

References 19 publications

Endothelium-dependent and independent vasodilation studied at normoglycaemia in Type I diabetes mellitus with and without microalbuminuria

Endothelium-dependent and independent vasodilation studied at normoglycaemia in Type I diabetes mellitus with and without microalbuminuria

Thiamine corrects delayed replication and decreases production of lactate and advanced glycation end-products in bovine retinal and human umbilical vein endothelial cells cultured under high glucose conditions

Nitric oxide and vascular responses in Type I diabetes

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