Effect of Somatostatin on Plasma Glucose and Insulin Responses to Glucagon and Tolbutamide in Man

Abstract

To characterize further the mechanism by which somatostatin lowers plasma glucose levels in man, we studied its effect on glucagon-induced glycogenolysis in 6 normal subjects. Additionally, we examined the effect of somatostatin on glucagonand tolbutamide-stimulated insulin release. During infusion of somatostatin (250 μg iv bolus followed by a sustained infusion of 500 μg/hr), plasma glucose responses to glucagon (1 mg iv) exceeded those seen after glucagon administration alone. The resultant hyperglycemia (190–200 mg/100 ml) was unaffected by administration of tolbutamide (1 g iv) and persisted for 15 min after stopping the somatostatin infusion. Plasma insulin remained at basal levels throughout the infusion, despite administration of glucagon and tolbutamide (with coexistent hyperglycemia). Within 15 min after stopping the somatostatin infusion, plasma insulin rose abruptly and plasma glucose declined toward basal levels. These studies indicate that, in man: 1) the hypoglycemic effect of somatostatin is not due to impaired hepatic responsiveness to glycogenolytic stimulation; 2) somatostatin inhibits insulin responses to glucagon, tolbutamide, and hyperglycemia; 3) the acute hypoglycemic effect of tolbutamide depends on insulin secretion; and 4) somatostatin administration may cause further deterioration of glucose tolerance in diabetic patients not receiving exogenous insulin.