Effects of Hypoglycemia on Glucose 6 Phosphatase, Nogo 66 Receptor Gene Expression in Cerebellum and Walk Performance in Ladder Rung Walking of Streptozotocin Induced Diabetic Rats

Abstract

Brain is dependent on a continual supply of glucose diffusing from the blood. Hence low amount of blood glucose affect the brain first. Subtle reduction of cognitive efficiency is one of common side effect of hypoglycaemia can be observed when the glucose falls below 65 mg/dl. So Glucose homeostasis in humans is a critical factor for the functioning of nervous system. Hypoglycemia, diabetic hypoglycemia and hyperglycemia are found to be associated with central and peripheral nerve system dysfunction. Hyperglycemia and hypoglycemia induces oxidative stress in neurons and results in activation of multiple biochemical pathways. These activated pathways are a major source of damage and are potential therapeutic targets in neuropathy. In the present study, the effects of insulin induced hypoglycemia and hyperglycemia was studied on the Glucose 6 phosphatase and NOGO 66 receptor. A single intrafemoral dose (50 mg/kg body weight) of streptozotocin was administered to induce diabetes. Hypoglycaemia was induced by appropriate doses of insulin subcutaneously in control (1.5 Unit/Kg body weight) and diabetic rats (10 Unit/Kg body weight). Glucose 6 phosphatase is a key enzyme in systemic glucose homeostasis. Specific enzyme activity of Glucose 6 phosphatase was studied spectrophotometrically in different experimental groups in liver and cerebral cortex region. Results showed decreased Glucose 6 phosphatase activity in D (p<0.001) than C group and increase in D+IIH (p<0.001) and C+IIH (p<0.001) groups compare to C and D group. Total RNA was obtained. cDNA was prepared successfully but gene could not amplified of NOGO 66 since it requires further optimisation. Behaviour study was carried out in control and experimental group of rats to asses motor skill and motor coordination. Ladder rung walking test was done. Regular and irregular pattern of ladder were used to check motor coordination and learning skills in control and experimental group. Results conclude motor coordination impairment in D and Hypoglycemic groups than C group. Rate of ladder crossing is less in D, C+IIH and D+IIH compare to C group in both regular and irregular pattern. Foot fault scoring of D, C+IIH and D+IIH is found more than C group which shows motor impairment. Walk performance scoring is found low in hypoglycaemia and hyperglycemia, lowest in D and D+IIH group suggesting impairment in their ability to integrate sensory input with appropriate motor commands to balance their posture on ladder. Motor coordination impairment results Abstract suggested causing cognitive impairment and motor dysfunction. These results conclude that hyperglycemia and hypoglycemia causes prominent imbalance in rate of walking, griping and coordination of limbs which eventually affect the motor coordination and cognitive efficiency. These motor deficits due to hypoglycaemia and hyperglycemia may eventually results in neuropathy. Key words C-control D-diabetic C+IIH-Insulin induced hypoglycemia in control rats D+IIH-Insulin induced hypoglycemia in diabetic rats