Incidence of Hypoglycemia in Diabetic population and the Effect of Hypoglycemia on the gene expression of NRG 1 and ErbB 2 receptor in Streptozotocin induced Diabetic Rats

Abstract

Glucose homeostasis in humans is a critical factor for the functioning of nervous system. Hypoglycemia and hyperglycemia is found to be associated with central and peripheral nerve system dysfunction. In the present study, we surveyed the incidence of hypoglycemic events and complications associated with diabetes, occurring in diabetic patients in cross section of population in Ahmedabad. We also investigated the effects of insulin induced hypoglycemia and streptozotocin induced diabetes on the SDH, NRG 1 and ErbB 2 receptor. A single intrafemoral dose of streptozotocin was administered to induce diabetes. Hypoglycaemia was induced by appropriate doses of insulin subcutaneously in control and diabetic rats. The kinetic parameters Vmax and Km of SDH were studied spectrophotometrically at different substrate concentrations of fructose. Results showed enhanced SDH activity in D (p<0.001) and D+IIH (p<0.001) group than C group and decrease in D+IIH (p<0.001) and C+IIH (p<0.001) groups compare to D group. NRG 1 gene expression was not obtained due to some experimental condition but ErbB 2 receptor gene expression obtained and showed a downregulation in diabetic and hypoglycemic groups of rats compare to C group and also showed downregulated expression in both D+IIH and C+IIH group compare to D group in cerebral cortex. While in cerebellum and brain stem upregulation of ErbB 2 receptor gene expression were observed in D, C+IIH and D+IIH groups compared to C group and D+IIH group showed increase Erb 2 expression compared to D group. These studies demonstrated that a fluctuation in glucose leads to functional disturbance in the neuronal ErbB 2 in the cerebral cortex, cerebellum and brain stem during insulin induced hypoglycemia in diabetic rats. Incline beam test result conclude motor coordination impairment in Diabetic and Hypoglycemic groups than Control. Altered expression of ErbB 2 in cerebral cortex, cerebellum and brain stem of diabetic and hypoglycemic rats along with motor coordination impairment results suggested causing cognitive impairment and motor dysfunction. These results conclude that the expression of ErbB 2 is functionally compromised during hyperglycemia and hypoglycemia compared to hyperglycemia, hypoglycemia causes prominent imbalance in ErbB 2 activity which is suggested to be involved in demyelination, hypermyelination and dysfunction associated with hypoglycemia.