Effect of Insulin Treatment on Heregulin Mediated Remyelination in Diabetic Rats

Abstract

Glucose homeostasis has a significant role in the overall functioning of the nervous system. During hyperglycaemia the oxidative stress induced in the cell triggers various metabolic pathways capable of inducing damage to cell. Diabetic neuropathy encompasses a group of nervous system disorders and demyelination is one of its important complications. Remyelination in central nervous system is a difficult task as compared to Peripheral nervous system. In CNS, the NRG 1 -ErbB signalling pathway induces remyelination by promoting the survival and differentiation of myelin producing Oligodendrocytes. Heregulin (type I, NRG 1) and insulin both enhances the survival and differentiation of oligodendrocytes by inducing PI3/Akt pathway. In this study we hypothesised that the low insulin level could alter the Heregulin gene expression and subsequently remyelination of defected neurons. A significant increase in food, water consumption and blood glucose level was observed in diabetic rats when compared with control group of rats. Glucose deficiency within the cell and glycosuria resulted in this increase and the decrease in body weight of diabetic rats could be an indication of excessive fat metabolism. The insulin treatment given to D+I group, brought down the readings near to control group. Blood glucose levels were also found to be higher in diabetic rats due to the lack of insulin. Motor impairment in diabetic rats were assessed by modified ladder rung test on the basis of foot fault scoring and calculation of total time and immobile time. Diabetic rats were having highest foot fault and immobile time suggesting their impaired motor function. Specific activity of Glucose-6-Phosphatase was assayed in Liver, Muscle and Cerebral Cortex. The activity of this enzyme was found elevated in both diabetic and D+I group when compared with control rats. Also from the PCR results ,it was clear that the Heregulin gene expression gets down regulated during diabetes and the insulin treatment given to D+I group resulted in an up regulation of this gene suggesting that insulin plays a crucial role in the expression of Heregulin gene.