Arginine-induced glucagon secretion and glucagon-induced enhancement of amino acid catabolism are not influenced by ambient glucose levels in mice

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Amino acids stimulate the secretion of glucagon, and glucagon receptor signaling regulates amino acid catabolism via ureagenesis, together constituting the liver-alpha cell axis. Impairment of the liver-alpha cell axis is observed in metabolic diseases such as diabetes. It is, however, unknown whether glucose affects the liver-alpha cell axis. We investigated the role of glucose on the liver-alpha cell axis in vivo and ex vivo. The isolated perfused mouse pancreas was used to evaluate the direct effect of low (3.5 mmol/L) and high (15 mmol/L) glucose levels on amino acid (10 mmol/L arginine)-induced glucagon secretion. High glucose levels alone lowered glucagon secretion, but the amino acid-induced glucagon responses were similar in high and low glucose conditions (p=0.38). The direct effect of glucose on glucagon and amino acid-induced ureagenesis was assessed using isolated perfused mouse livers stimulated with a mixture of amino acids (Vamin R, 10 mmol/L) and glucagon (10 nmol/L) during high and low glucose conditions. Urea production increased robustly but was independent of glucose levels (p=0.95). To investigate the whole-body effects of glucose on the liver-alpha cell axis, four groups of mice received intraperitoneal injections of glucose-vamin (2 g/kg, + 3.5 µmol/g, respectively, G/V), saline-vamin (S/V), glucose-saline (G/S), or saline-saline (S/S). Blood glucose did not differ significantly between G/S and G/V groups. Levels of glucagon and amino acids were similar in the G/V and S/V groups (p=0.28). Amino acids may overrule the inhibitory effect of glucose on glucagon secretion and the liver-alpha cell axis may operate independently of glucose in mice.

TidsskriftAmerican Journal of Physiology - Endocrinology and Metabolism
Sider (fra-til)E207–E214
StatusUdgivet - 2022

ID: 314444183