Effect of intermittent physiologic hyperglucagonemia on postprandial plasma glucose levels in normal man

The ability of glucagon to impair glucose tolerance has been questioned by studies involving infusion of exogenous glucagon during a glucose load. Since such hormone administration may not reflect the physiologic pattern of glucagon secretion and may result in hepatic downregulation to glucagon, the present experiments have examined the effects of intermittent endogenous hyperglucagonemia (induced by episodic infusion or arginine) on plasma glucose profiles of normal man following ingestion of mixed meals. In control studies following meal ingestion, plasma glucose, insulin and glucagon increased respectively 15-30 mg/dl, 30-60 uU/ml and 25-50 pg/ml. When meals were accompanied by arginine infusions, plasma glucagon responses were augmented three to fourfold (p less than 0.05). Amplitudes of glycemic excursions during infusion of arginine (345 +/- 40 mg/dl) were significantly augmented compared to those observed in control studies (286 +/- 34 mg/dl, p less than 0.02). These results indicate that intermittent increases in plasma glucagon within the physiologic range can adversely affect postprandial glucose profiles in normal man despite concomitant hyperinsulinemia and suggest that such hyperglucagonemia may contribute to impaired postprandial glucose tolerance in diabetic individuals in whom insulin secretion is deficient.