Abstract
In this research Sorbitol dehydrogenase (SDH) was partially purified from sera of patients with type I diabetes mellitus by dialysis and ion exchange chromatography step by step. One peak of SDH activity was obtained with specific activity of 40.065 unit/mg protein and with purification fold of 98.9 compared to crud enzyme. Inhibition of SDH was studied by Glibenclamide and Rosiglitazone drugs, the best concentration of both inhibiters was 6mM. The mechanism of SDH inhibition by using both drugs were noncompetitive. There is no change in Km value 100 mM. Vmax value without inhibitor was 22.175 but 13.634 and 14.615 unit/ml with Glibenclamide and Rosiglitazone respectively. Accordingly, the inhibition constant Ki was calculated and appeared 7mM for both inhibitors above. Finally, we propose that action of these drugs may contribute to decrease patients with type I diabetes complications through inhibition SDH which plays an important role in polyol pathway.
Highlights
Diabetes mellitus is a heterogeneous metabolic disorder characterized hyperglycemia resulting from defective insulin secretion, resistance to insulin action or both(1)
High levels of Sorbitol dehydrogenase (SDH) activity lead to increasing fructose availability(8) which plays an important role in the pathogenesis of diabetic complications (6)
The aim of this study is inhibition of SDH activity which plays an important role in polyol pathway
Summary
Diabetes mellitus is a heterogeneous metabolic disorder characterized hyperglycemia resulting from defective insulin secretion, resistance to insulin action or both(1). In the first of these, the enzyme aldos reductase reduced glucose to sugar alchohol sorbitol using NADPH as a cofactor (4), the increased glucose concentration is associated with the increase of polyol pathway activity(5). SDH, the second enzyme in the polyol pathway, oxidizes sorbitol to fructose in the presence of NAD+ and the enzyme SDH is considered an important part in this pathway. High levels of SDH activity lead to increasing fructose availability(8) which plays an important role in the pathogenesis of diabetic complications (6).
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