Evidence for a physiologic role of pancreatic glucagon in human glucose homeostasis: studies with somatostatin.

To study the role of glucagon in human glucose homeostasis, experimental glucagon deficiency was produced by infusing somatostatin (i. v. 250 mug bolus, followed by infusion of 500 mug/hr) in six normal subjects and in two hypophysectomized patients-an insulin-dependent diabetic and a nondiabetic. In normal subjects, somatostatin lowered plasma glucagon from a mean (plus or minus SE) basal level of 85 plus or minus 15 to 33 plus or minus 10 pg/ml, p smaller than 0.001. Concurrently, plasma glucose fell from 90 plus or minus 2 to 73 plus or minus 3 mg/100 ml, p smaller than 0.001. Serum insulin and growth hormone fell slightly during somatostatin infusion, while plasma free fatty acids rose. In both hypophysectomized patients, somatostatin lowered plasma glucagon and glucose levels. In all subjects, after stopping somatostatin infusions, plasma glucagon and glucose returned promptly to control values, while serum growth hormone did not change. In additional in vitro studies, somatostatin (1 mug/ml) had no effect on muscle glucose uptake. Since it is known that somatostatin has no direct effect on hepatic glucose production, these results suggest that the fall in plasma glucose during somatostatin infusion resulted from inhibition of glucagon secretion, thus providing evidence that this hormone plays a physiologic role in the maintenance of fasting euglycemia in man.