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Udgivet

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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Galsgaard KD, Jepsen SL, Kjeldsen SA, Pedersen J, Wewer Albrechtsen NJ, Holst JJ. Alanine, arginine, cysteine, and proline, but not glutamine, are substrates for, and acute mediators of, the liver-α-cell axis in female mice. Am J Physiol Endocrinol Metab 318: E920 E929, 2020. First published April 7, 2020; doi:10.1152/ ajpendo.00459.2019. 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.

OriginalsprogEngelsk
TidsskriftAmerican Journal of Physiology: Endocrinology and Metabolism
Vol/bind318
Udgave nummer6
Sider (fra-til)E920-E929
ISSN0193-1849
DOI
StatusUdgivet - 1 mar. 2020

ID: 59662886