THE HYPOGLYCEMIC RESPONSE TO INSULIN IN MAN AFTER SULFONYLUREA BY MOUTH*

Abstract

IT IS now fairly well established that the sulfonylureas are effective in reducing the hyperglycemia of many patients with diabetes mellitus, especially those in whom the diabetes developed after 40 years of age (1–4). The precise mechanism whereby the sulfonamide derivatives produce a reduction in the blood sugar of animal and man is still unknown. There is general agreement that these compounds do not elicit a hypoglycemic response in the totally depancreatized dog (5) and the severely diabetic alloxanized rat (6). Accordingly, the hypoglycemic response is dependent upon the integrity of the beta cells of the islets of Langerhans and the presence of insulin. Further, the response cannot be due to a diminution in the availability or activity of glucagon, since the alpha cells of the islets of Langerhans are relatively intact in the alloxanized animal. Likewise, the response cannot be due to some nonspecific hepatotoxic effect or a decrease in the activity of the anterior pituitary or adrenal cortex, since such actions would be present in the alloxanized as well as in the normal rat.