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 - Albrechtsen, Nicolai J. Wewer

AU - Holst, Jens J.

PY - 2020

Y1 - 2020

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 mu mol/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 I (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-a-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 mu mol/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 I (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-a-cell axis in female mice, as they all increased glucagon secretion and their disappearance rate was altered by GRA.

KW - amino acids

KW - alpha-cell

KW - glucagon

KW - liver-alpha-cell axis

KW - AMINO-ACID TRANSPORT

KW - UREA-CYCLE ENZYMES

KW - GLUCAGON-SECRETION

KW - RAT-LIVER

KW - GLUCOSE

KW - INSULIN

KW - STIMULATION

KW - RECEPTOR

KW - DISRUPTION

KW - INFUSION

U2 - 10.1152/ajpendo.00459.2019

DO - 10.1152/ajpendo.00459.2019

M3 - Journal article

C2 - 32255678

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 -