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

Abstract

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 (VaminR, 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.

Deficiency of the metabolic enzyme SCHAD in pancreatic β-cells promotes amino acid–sensitive hypoglycemia

“…5 A ). The concurrent rise in glucose and insulin is not unique to our study as also others have reported that amino acid injection in mice results in increased glucose levels ( 27 , 28 ). Whether this is potentially due to increased glucagon output from the islets requires further study.…”

Glucagon receptor antagonism impairs and glucagon receptor agonism enhances triglycerides metabolism in mice

“…Livers from C57bl/6JRj male and female mice, 10–12 weeks of age, were perfused to investigate any direct effects of glucagon on hepatic lipolysis. Detailed description of the liver perfusion setup including the surgery can be found in [ 17 ].…”

Theobroma cacao fortified-feed ameliorates potassium bromate-induced oxidative damage in male Wistar rat

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