Normal Syrian hamsters were given daily intraperitoneal injections of tolbutamide sodium or 0.9 per cent NaCl solution. Normal albino rats were fed a control or a glyburide (HB-419) containing diet. After seven weeks of treatment, the animals were killed, the pancreatic islets were isolated by collagenase digestion and their diameter and secretory activity in vitro were measured. In other animals, the total pancreatic acid-alcohol extractable insulin was measured. In control animals, there was a linear relationship · between body weight on the one hand and pancreatic insulin content on the other. In animals previously treated with tolbutamide, at the dose of 63 mg./kg., the relationships between these two variables were altered: a slight increase in body weight was accompanied by a decrease in pancreatic insulin content. The islets of animals treated with either drug released less insulin in vitro than those of control animals; the degree of B cell depression was related to the dose of tolbutamide which the animals had received. All drug-induced abnormalities disappeared approximately one week after the cessation of treatment. The possible significance of these observations to human therapy is discussed.

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