Abstract
Eight healthy subjects were studied 3 times serially at 1 week intervals. Blood glucose and plasma insulin were investigated for 240 minutes after oral administration of 40, 80 or 120 mg of gliclazide. Blood glucose fell significantly with all of these doses of gliclazide. The decrease in blood glucose induced by the administration of gliclazide was significnatly greater than that observed in the control group without the drug. Plasma insulin rose significantly after the administration of either 80 or 120 mg of the drug, while the mean increment of plasma insulin was not remarkable in the case of 40 mg, probably because of the dilution by systemic circulation. It was demonstrated that both the maximum increase in insulin and the maximum decrease in blood glucose were pro. portional to the dosage of gliclazide.
Experimental studies were performed using a preparation of in situ local circulation of the pancreas in dogs. Gliclazide was infused into the superior pancreatic artery in amount of 10, 20 or 40 mg for 10 minutes. The plasma levels of insulin and glucagon were assayed in the blood obtained from the pancreatic vein and the blood glucose levels in the femoral artery were determined simultaneously, A significant rise of plasma insulin was observed with either dose of gliclazide, but no remerkable change was observed in the glucagon or in the blood glucose. Thus, the following were confirmed: 1) gliclazide has hypoglycemic action in man, 2) gliclazide causes insulin release in man and dogs, and 3) gliclazide does not inhibit the secretion of pancreatic glucagon in dogs. Gliclazide is one oi the unquestionable hypoglycemic agents and this action is thought to be brought about mainly 133, insulin release in response to the drug, although our results cannot exclude any extrapancreatic action of the crug.
