Abstract Context Amino acids are known to stimulate glucagon secretion and most amino acids can elicit a glucagon response after intravenous administration. Recent studies have identified a feedback loop between the liver and pancreatic alpha cells, regulated by glucagon and circulating amino acids, termed the liver-alpha cell axis. Objective We compared the glucagonotropic effects of amino acids suggested to drive the liver-alpha 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 ± standard deviation 133 ± 71 vs. 34 ± 34 pmol/L × min) and the maximum concentration of glucagon after injection (44 ± 18 vs. 15 ± 4 pmol/L) (P 0.01 for both). Alanine injection resulted in a minor increase in the peak concentration of glucagon, while glutamine showed a non-significant trend towards increased glucagon secretion. Insulin secretion was significantly increased by injections of arginine, alanine, and glutamine, with leucine showing a non-significant trend. 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-alpha cell axis in humans.
Suppli et al. (Sat,) studied this question.
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