Failure of Prolonged Sulfonylurea Administration to Enhance Insulogenic Response to Glycemic Stimulus

The effect of chronic administration of sulfonylurea compounds on the insulogenic responsiveness of beta cells was studied in normal dogs who received hypoglycemia-maintaining dosages of tolbutamide daily for several weeks. Insulin concentration in pancreaticoduodenal venous blood was measured during infusion of glucose at a rate causing physiologic increase in arterial glucose concentration. Neither fasting plasma insulin level nor its enhancement during progressive hyperglycemia was significantly greater in tolbutamide-treated animals than in the control group. The data indicate that prolonged exposure of nondiabetic canine beta cells to effective concentrations of sulfonylurea does not increase their insulin-secretory responsiveness to glycemic stimulus. Whether these agents impinge similarly or differently upon diabetic human islets awaits elucidation. It was parenthetically observed that dogs treated with tolbutamide for several weeks required more than twice the usual amount of Nembutal to maintain surgical anesthesia.