Glucagon and Amino Acid Metabolism

Abstract

Glucagon is thought to play two major metabolic roles (UNGER and ORCI 1981). One, as shown over 30 years ago by Sutherland and associates (Sutherland 1950; Sutherland et al. 1968), is to increase blood glucose levels by initiating hepatic glycogenolysis. The other is to promote gluconeogenesis, thus serving to maintain glucose production, even in the face of increased insulin levels, such as after a high protein meal when insulin and glucagon are both increased. Therefore, glucagon has a very significant metabolic role, especially in carbohydrate deficiency, be it in the fed or in the fasted state. Glucagon has also been found to decrease amino acid levels after its infusion in humans (Fig. 1) and experimental animals (Helmer et al. 1957; Weinges 1959; Landau and Lugibihl 1960; Bromer and Chance 1969; Marliss et al. 1970; Aoki et al. 1974). This effect is apparent in subjects with glucagon-producing tumors, who have been found to have strikingly low concentrations of all or almost all amino acids (Mallinson et al. 1974; Holst 1978, 1979; Kessinger et al. 1977; Boden et al. 1978; Riddle et al. 1978; Holst et al. 1979; Stacpoole et al. 1981; Bhathena et al. 1981). This response could result both from increased hepatic amino acid trapping and, possibly, from a global effect of glucagon in regulating the gradients of amino acids across all cells, or even in regulating protein synthesis and breakdown.