Abnormal alpha cell function in human diabetes. The response to oral protein

The response of immunoreactive glucagon (IRG) to a protein meal and the effects of hyperglycemia and/or hyperinsulinemia on this response were studied in patients with adult and juvenile-type diabetes and in nondiabetic subjects. In nondiabetic subjects, hyperglycemia induced by intravenously administered glucose abolished or reduced the protein-induced increase in IRG. In subjects with adult-type diabetes made normoglycemic by the overnight administration of insulin (1 U/hour), the IRG response to protein was the same as when they were hyperglycemic, whereas in subjects with juvenile-type diabetes overnight insulin infusion restored the response to normal. In juvenile-type diabetic subjects, hyperglycemia induced during insulin infusion did not reduce the IRG response to protein, but the administration of additional insulin during hyperglycemia lowered it. In adult-type diabetic subjects, hyperglycemia during insulin infusion reduced the IRG response, but the administration of additional insulin did not lower it further. In both groups of diabetic subjects, the protein-induced increase in IRG was accompanied by a significant 50 mg/dl increase in plasma glucose in 2 hours despite a constant infusion of insulin. It is concluded that in subjects with adult-type diabetes the IRG response to protein is uninfluenced by insulin whereas in those with juvenile-type diabetes the defect is virtually restored to normal by insulin. The increase in plasma glucose associated with the protein-induced increase in IRG despite a constant insulin infusion suggests that an increase in glucagon, when unaccompanied by an increase in insulin, contributes to the postprandial hyperglycemia of diabetes.