Abnormal response of pancreatic glucagon to glycemic changes in diabetes mellitus

In order to determine pancreatic alpha cell function in diabetes mellitus, plasma glucagon responses to either an oral glucose load or insulin-induced hypoglycemia were investigated. Plasma glucagon in 6 normal control subjects fell significantly after the administration of glucose, whereas the levels of plasma glucagon did not decrease after glucose ingestion in patients with diabetes mellitus. In the group with severe diabetes, whose fasting blood glucose exceeded 200 mg/100 ml, the plasma glucagon level rose after glucose administration instead of decreasing. In 6 patients with diabetes mellitus, plasma glucagon did not decrease but rather increased during a glucose tolerance test which was performed after treatment with insulin and/or diet. In 6 control subjects, there was a remarkable rise of plasma glucagon in response to insulin-induced hypoglycemia. In contrast, no significant rise in plasma glucagon was demonstrated in 19 diabetic subjects undergoing intravenous insulin test. Seven patients, in whom an insulin test was repeated after treatment with insulin, sulfonylurea, or diet had a small rise in peak plasma glucagon and an increase in the integrated area under the glucagon response curve. It is concluded that the abnormal glucagon response to changes in blood glucose might be a primary defect in diabetes mellitus.