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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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@article{a35193bd59474202808028f229acd3d9,
title = "Alanine, arginine, cysteine, and proline, but not glutamine, are substrates for, and acute mediators of, the liver-α-cell axis in female mice",
abstract = "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.",
keywords = "amino acids, glucagon, liver-α-cell axis, α-cell",
author = "Galsgaard, {Katrine D} and Jepsen, {Sara L} and Kjeldsen, {Sasha A S} and Jens Pedersen and {Wewer Albrechtsen}, {Nicolai J} and Holst, {Jens J}",
year = "2020",
month = "6",
day = "1",
doi = "10.1152/ajpendo.00459.2019",
language = "English",
volume = "318",
pages = "E920--E929",
journal = "American Journal of Physiology: Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "6",

}

RIS

TY - JOUR

T1 - Alanine, arginine, cysteine, and proline, but not glutamine, are substrates for, and acute mediators of, the liver-α-cell axis in female mice

AU - Galsgaard, Katrine D

AU - Jepsen, Sara L

AU - Kjeldsen, Sasha A S

AU - Pedersen, Jens

AU - Wewer Albrechtsen, Nicolai J

AU - Holst, Jens J

PY - 2020/6/1

Y1 - 2020/6/1

N2 - 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.

AB - 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.

KW - amino acids

KW - glucagon

KW - liver-α-cell axis

KW - α-cell

U2 - 10.1152/ajpendo.00459.2019

DO - 10.1152/ajpendo.00459.2019

M3 - Journal article

VL - 318

SP - E920-E929

JO - American Journal of Physiology: Endocrinology and Metabolism

JF - American Journal of Physiology: Endocrinology and Metabolism

SN - 0193-1849

IS - 6

ER -

ID: 59662886