Regulatory Action of Nitric Oxide on Insulin Secretion in the Rat Pancreas

Kim, Myung Jun; Park, In Sun

Abstract

nitric oxide (NO) has been known as a cytotoxic free radical or a messenger molecule in various tissues of the body. Recently, this small molecule was reported to be associated with secretory function of glandular tissues. Although it is very likely that NO modulates the pancreatic secretion, little is known about its accurate mechanism of action. We, thus, attempted to reveal the action of NO on insulin secretion by analyzing insulin immunoreactivity and its mRNA expression in the pancreatic islet of the rats treated with NAME (L-N(G)-nitroarginine methyl ester), a NOS inhibitor. Male Sprague-Dawley rats (150~200 g, body weight) with normal blood glucose level (80~120 mg/dl) were assign-ed into normal control group and the experimental ones. NAME was injected into jugular vein of the rats by cannula-tion using polyethylene tube. We have examined blood glucose level at every 30 minutes for 2 hours after NAME injection. Other rats were killed at every 30 minutes for 2 hours following the NAME treatment, and the pancreatic tissues were taken in order to analyze the changes of insulin contents and insulin mRNA expression with the techniques of immunocytochemistry and in situ hybridization. The present experiments showed that intrapancreatic NO influence insulin secretion in the pancreatic islets. Blood glucose concentration was decreased for initial 90 minutes after NAME injection, then, recovered towards normogly-cemic state. Immunocytochemical staining demonstrated that a slight increase of insulin immunoreactivity was found in some Langerhans islets of the NAME-treated rats. On the contrary, we found a considerable increase of insulin mRNA expression in the NAME-treated rats compared to the control one. Based on the results of the present experiments, we suggest that NO is a potent and endogenous modulator of insulin secretion, and a lowered level of NO in pancreatic tissue stimulates insulin synthesis in beta cells by promoting transcrip-tion of insulin DNA.