Abstract

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia due to insufficient secretion or action of insulin.Elevated oxidative stress and diminished antioxidants may play an important role to develop T2DM and its complications. Aldose reductase (AR) enzyme plays a key role in the reduction of glucose to sorbitol by Polyol pathway. To estimate the AR activity and malondialdehyde (MDA) levels and in patients with T2DM. In this case-control study, a total number of 60 subjects (30 T2DM and 30 age-matched controls) wererecruited.Fasting blood sugar (FBS), Post-Prandial blood sugar (PPBS), AR activity and MDA levels were estimated in all the subjects. The AR activity was estimated by nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidation method. The plasma MDA levels were estimated by the thiobarbituric acid reactive substance (TBARS) method. For Statistical analysis, all the data were compared between the two groups by using unpaired t-test. Pearson correlation coefficient was calculated among T2DM. A P value <0.05 was considered as statistically significant for all data analyzed. The mean of FBS, PPBS, AR activity, and MDA levels were found significantly high in T2DM as compared to controls (P<0.001, P<0.001, P<0.001, P<0.001, respectively). A significant positive correlation was found between FBS and PPBS among T2DM (r=0.71, P<0.01). However, There was no significant correlation found between AR activity and MDA level among T2DM (r=0.002, P>0.05). Results showed thatthe mean of FBS, PPBS, AR activity, and MDA levels were found significantly higher in T2DM than controls. There was no significant correlation found between AR activity and MDA level among T2DM.

Highlights

  • Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia due to insufficient secretion or action of insulin.Elevated oxidative stress and diminished antioxidants may play an important role to develop T2DM and its complications

  • There was no significant correlation found between Aldose reductase (AR) activity and MDA level among T2DM (r=0.002, P>0.05)

  • Studies reported that T2DM revealed oxidative stress load, oxidative destruction of sub-cellular membrane lipids has been implicated along with other types of intracellular oxidative damage in the normal aging process and in the pathophysiology of a number of chronic illnesses[11, 12].Glucose oxidation is the main source of free radicals generation.The polyol pathway leads to the reduction of glucose to sorbitol via aldose reductase (AR) enzyme in an nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) dependent manner

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Summary

Introduction

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia due to insufficient secretion or action of insulin.Elevated oxidative stress and diminished antioxidants may play an important role to develop T2DM and its complications. Studies reported that T2DM revealed oxidative stress load, oxidative destruction of sub-cellular membrane lipids has been implicated along with other types of intracellular oxidative damage in the normal aging process and in the pathophysiology of a number of chronic illnesses[11, 12].Glucose oxidation is the main source of free radicals generation.The polyol pathway leads to the reduction of glucose to sorbitol via aldose reductase (AR) enzyme in an nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) dependent manner. 13-16 Increased glucose pumped by the polyol pathway does not produce ROS directly but contributes greatly to an overall redox imbalance in the cell that leads to oxidative stress17summarized in Figure 1.More than 30% of the glucose pumped into the polyol pathway causing a significant depletion of NADPH and as a result a significant decrease in the GSH level. MDA has been an established biomarker of free radical-mediated lipid damage and oxidative stress[20]

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