Effect fo Nitric Oxide on Control of Insulin Secretion in Rat Pancreas / 대한내분비학회지

BACKGROUND: NO (nitric oxide), derived from L-arginine through the action of nitric oxide synthase (NOS), is a short-lived free radical transmitting cellular signals for vasodilation, neurotransmission, and cytotoxicity. Recently, this molecule has been reported to be involved in the various glandular secretion. Although the relationship between NO and the pancreatic endocrine secretion has been widely investigated, the role of NO on insulin secretion has not been elucidated. Therefore, the present study was designed to reveal the precise action of NO on the secretion and synthesis of insulin following administration of NAME (L-NG -nitroarginine methyl ester) or L-arginine using immunocytochemistry and in situ hybridization techniques. METHODS: NAME or L-arginine was administered into jugular vein of the male Sprague-Dawley rat (180~200 g, b,w.) exhibiting normoglycemia (80~120mg/dL). Blood glucose concentrations were measured at intervals of 30 minutes for 2 hours after drug treatment. The pancreatic tissues were taken out at 30 and 90 minutes following drugs administration for insulin immunocytochemistry and in situ hybridization. RESULTS: Both NAME and L-arginine treatments diminished blood glucose levels. The decrease of blood glucose level was more prominent in NAME-treated rats than that of L-arginine. Insulin immunoreactivity in drugs-treated rat pancreas decreased compared to that in normal control, while the expression of insulin mRNA was significantly increased. CONCLUSION: On the basis of present study, it is concluded that the transient changes of NO con-centration, regardless of increase or decrease, in Langerhans islet might act as a potent stimulant in insulin secretion and its synthesis.

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

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.