The enhancement of peripheral glucose utilization by glucagon.

During the past 30 years evidence has been accumulating which suggests that glucagon (the hyperglycemic-glycogenolytic factor of the pancreas) is a true hormone and that it is produced in the Islets of Langerhans (1, 2). Its purification and crystallization were finally accomplished in 1953 by Staub, Sinn, and Behrens (3). The crystalline material is a simple protein with a molecular weight of approximately 4,200 and an amino acid composition which differs in important ways from that of insulin (4). This establishes glucagon as an entity distinct from insulin. Crystalline glucagon is an extremely active substance. In the cat, 0.05 y per Kg. body weight causes a significant rise in blood sugar which lasts 25 minutes (4). Sutherland, Cori, Wosilait, and Rall (5, 6) have shown that glucagon stimulates the synthesis of active phosphorylase in the liver. This enzyme catalyzes the rate-limiting reaction (glycogen ;± glucose-i-phosphate) in the transformation of glycogen to glucose. The effect of glucagon on liver phosphorylase adequately explains its well-known hyperglycemic-glycogenolytic action. With respect to its role in carbohydrate metabolism, some investigators look upon glucagon as an insulin antagonist (1, 2, 7) while others consider it an insulin synergist (8, 9). Still others are skeptical of its hormonal nature (10, 11). In the present paper experiments are reported which indicate that glucagon, in addition to mobilizing liver glycogen, increases the peripheral utilization of glucose."