Intravenous Arginine Stimulates Glucagon Secretion More Than Equimolar Alanine, Leucine, Glutamine, and Proline in Humans.

Context: Amino acids are known to stimulate glucagon secretion, and most amino acids can elicit a glucagon response after IV administration. Recent studies have identified a feedback loop between the liver and pancreatic α cells, regulated by glucagon and circulating amino acids, termed the liver-α cell axis. Objective: We compared the glucagonotropic effects of amino acids suggested to drive the liver-α cell axis in humans. Methods: We recruited 12 healthy male participants for a double-blind, randomized study. Each participant received equimolar bolus injections of alanine, arginine, leucine, glutamine, proline, and saline (placebo) after an overnight fast on separate days. Results: Arginine significantly increased glucagon plasma concentrations compared to placebo, evaluated by the incremental area under the curve after 30 minutes ([mean ± SD] 133 ± 71 vs 34 ± 34 pmol/L × min) and the maximum concentration of glucagon after injection (44 ± 18 vs 15 ± 4 pmol/L) ( Conclusion: In the given experimental setting, arginine was identified as the most efficient stimulator of glucagon secretion. Arginine, alanine, and glutamine stimulated insulin secretion, with arginine eliciting the largest response. Our results indicate that arginine could be involved in regulating the liver-α cell axis in humans.