Serotonergic receptor upregulation in cerebral cortex and down regulation in brainstem of streptozotocin induced diabetic rats: antagonism by pyridoxine and insulin

Abstract

Insulin secretion and glucose homeostasis is implicated through serotonergic function. Pyridoxine is involved in decarboxylation step in synthesis of serotonin. The present study was carried out to find the role of insulin in combination with pyridoxine on the concentrations of 5-HT and 5-HIAA, 5-HT receptor binding, 5-HTT gene expression and immunohistochemistry studies in the cerebral cortex and brainstem of streptozotocin induced diabetic rats. 5-HT content showed a significant decrease with a significant increase in 5-HIAA in cerebral cortex (p<0.01) and brain stem (p<0.001) in diabetic rats. 5-HT receptor binding parameters, B(max) and K(d), showed a significant decrease (p<0.001) in diabetic rats in cerebral cortex whereas in brainstem it showed a significant increase (p<0.001) compared to control. Gene expression studies of 5-HTT in cerebral cortex showed a significant down regulation (p<0.001) and in brainstem an upregulation (p<0.001) in diabetic rats compared to control. Insulin and pyridoxine treatment to diabetic rats reversed the 5-HT content, B(max), K(d) and gene expression of 5-HTT confirmed by immunohistochemistry studies in cerebral cortex and brainstem to near control. Thus our results suggest that pyridoxine along with insulin has a role in the regulation of insulin synthesis and release through serotonergic function which has clinical significance in the management of diabetes.