Secretion of Glucagon and Insulin in Hypophysectomized Rats: Effect of Tolbutamide

Abstract

Normal and hypophysectomized (hypox) rats, fed ad libitum, received intraperitoneal injections of tolbutamide (75 mg/kg/day) or of saline for 6 weeks. 24 h after the last injection, blood samples were taken for glucose, insulin and glucagon determinations. In normal rats, tolbutamide treatment did not alter serum glucose, insulin and glucagon, although it suppressed the secretion of insulin and glucagon by the pancreatic islets. In hypox rats, tolbutamide decreased serum glucose and insulin, elevated serum glucagon and stimulated the secretion of glucagon, but not that of insulin by the pancreatic islets. In addition, tolbutamide treatment increased the glucagon response to arginine in normal, but not in hypox rats. The serum glucose response to arginine was decreased by tolbutamide treatment and by hypophysectomy and, thus, appeared independent of the glucagon rise or preexisting glucagon level. We conclude that tolbutamide treatment decreased the secretion of glucagon and insulin in normal rats and stimulated that of glucagon in hypox rats, perhaps because of the low levels of insulin in the serum and in the pancreas of the latter. Our results are compatible with the hypothesis that the pancreatic action of tolbutamide is influenced by the pituitary.

Insulin Release in Rats 1 and 5 Days after Hypophysectomy

“…Glucose stimulated the secretion of insulin, but no quantitative conclusions could be drawn from this single experiment. Using the same preparation, insulin secretion was found decreased 3 weeks after hypophysectomy, while in a dynamic study the first phase of insulin release was found to be depressed 1 week and the second phase 5 weeks after removal of the pituitary gland [3], When pieces of rat pancreas or isolated islets were stimulated with glucose or tolbutamide, an impaired insulin biosynthesis and release was observed 3-13 weeks after hypophysectomy [2,4,[10][11][12].…”