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Alanine, arginine, cysteine, and proline, but not glutamine, are substrates for, and acute mediators of, the liver-α-cell axis in female mice

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The aim of this study was to identify the amino acids that stimulate glucagon secretion in mice and whose metabolism depends on glucagon receptor signaling. Pancreata of female C57BL/6JRj mice were perfused with 19 individual amino acids and pyruvate (at 10 mM), and secretion of glucagon was assessed using a specific glucagon radioimmunoassay. Separately, a glucagon receptor antagonist (GRA; 25-2648, 100 mg/kg) or vehicle was administered to female C57BL/6JRj mice 3 h before an intraperitoneal injection of four different isomolar amino acid mixtures (in total 7 µmol/g body wt) as follows: mixture 1 contained alanine, arginine, cysteine, and proline; mixture 2 contained aspartate, glutamate, histidine, and lysine; mixture 3 contained citrulline, methionine, serine, and threonine; and mixture 4 contained glutamine, leucine, isoleucine, and valine. Blood glucose, plasma glucagon, amino acid, and insulin concentrations were measured using well-characterized methodologies. Alanine ( P = 0.03), arginine ( P < 0.0001), cysteine ( P = 0.01), glycine ( P = 0.02), lysine ( P = 0.02), and proline ( P = 0.03), but not glutamine ( P = 0.9), stimulated glucagon secretion from the perfused mouse pancreas. However, when the four isomolar amino acid mixtures were administered in vivo, the four mixtures elicited similar glucagon responses ( P > 0.5). Plasma concentrations of total amino acids in vivo were higher after administration of GRA when mixture 1 ( P = 0.004) or mixture 3 ( P = 0.04) were injected. Our data suggest that alanine, arginine, cysteine, and proline, but not glutamine, are involved in the acute regulation of the liver-α-cell axis in female mice, as they all increased glucagon secretion and their disappearance rate was altered by GRA.

Original languageEnglish
JournalAmerican Journal of Physiology: Endocrinology and Metabolism
Volume318
Issue number6
Pages (from-to)E920-E929
ISSN0193-1849
DOIs
Publication statusPublished - 1 Jun 2020

    Research areas

  • amino acids, glucagon, liver-α-cell axis, α-cell

ID: 59662886