Portal infusion of amino acids is more efficient than peripheral infusion in stimulating liver protein synthesis at the same hepatic amino acid load in dogs

Dominique Dardevet, Scot R. Kimball, Leonard S. Jefferson, Alan D. Cherrington, Didier Rémond, Catherine A. DiCostanzo, Mary Courtney Moore

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Hepatic glucose uptake is enhanced by the portal delivery of glucose, which creates a negative arterioportal substrate gradient. Hepatic amino acid (AA) utilization may be regulated by the same phenomenon, but this has not been proven. Objective: We aimed to assess hepatic AA balance and protein synthesis with or without a negative arterioportal AA gradient. Design: Somatostatin was infused intravenously, and insulin and glucagon were replaced intraportally at 4- and 3-fold basal rates, respectively, in 3 groups (n = 9 each) of conscious dogs with catheters for hepatic balance measurement. Arterial glucose concentrations were clamped at 9 mmol/L. An AA mixture was infused intravenously to maintain basal concentrations (EuAA), intraportally to mimic the postmeal AA increase (PoAA), or intravenously (PeAA) to match the hepatic AA load in PoAA. Protein synthesis was assessed with a primed, continuous [ 14C]leucine infusion. Results: Net hepatic glucose uptake in the PoAA condition was ≤50% of that in the EuAA and PeAA conditions (P < 0.05). In the PoAA and PeAA conditions, hepatic intracellular leucine concentrations were 2- to 2.5-fold those in the EuAA condition (P < 0.05); net hepatic leucine uptake and [14C]leucine utilization were ≈2-fold greater (P < 0.05) and albumin synthesis was 30% greater (P < 0.05) in the PoAA condition than in the EuAA and PeAA conditions. Phosphorylation of ribosomal protein S6 [downstream of the mammalian target of Rapamycin complex 1 (mTORC1)] was significantly higher in the PoAA, but not PeAA, condition than in the EuAA condition. Conclusions: Portal, but not peripheral, AA delivery significantly enhanced hepatic protein synthesis under conditions in which AAs, glucose, insulin, and glucagon did not differ at the liver, an effect apparently mediated by mTORC1 signaling.

Original languageEnglish (US)
Pages (from-to)986-996
Number of pages11
JournalAmerican Journal of Clinical Nutrition
Volume88
Issue number4
StatePublished - Oct 1 2008

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Dogs
Amino Acids
Liver
Proteins
Leucine
Glucose
Glucagon
Ribosomal Protein S6
Insulin
Somatostatin
Albumins
Catheters
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

@article{f8bb416da8304dba8b63e3703953d27f,
title = "Portal infusion of amino acids is more efficient than peripheral infusion in stimulating liver protein synthesis at the same hepatic amino acid load in dogs",
abstract = "Background: Hepatic glucose uptake is enhanced by the portal delivery of glucose, which creates a negative arterioportal substrate gradient. Hepatic amino acid (AA) utilization may be regulated by the same phenomenon, but this has not been proven. Objective: We aimed to assess hepatic AA balance and protein synthesis with or without a negative arterioportal AA gradient. Design: Somatostatin was infused intravenously, and insulin and glucagon were replaced intraportally at 4- and 3-fold basal rates, respectively, in 3 groups (n = 9 each) of conscious dogs with catheters for hepatic balance measurement. Arterial glucose concentrations were clamped at 9 mmol/L. An AA mixture was infused intravenously to maintain basal concentrations (EuAA), intraportally to mimic the postmeal AA increase (PoAA), or intravenously (PeAA) to match the hepatic AA load in PoAA. Protein synthesis was assessed with a primed, continuous [ 14C]leucine infusion. Results: Net hepatic glucose uptake in the PoAA condition was ≤50{\%} of that in the EuAA and PeAA conditions (P < 0.05). In the PoAA and PeAA conditions, hepatic intracellular leucine concentrations were 2- to 2.5-fold those in the EuAA condition (P < 0.05); net hepatic leucine uptake and [14C]leucine utilization were ≈2-fold greater (P < 0.05) and albumin synthesis was 30{\%} greater (P < 0.05) in the PoAA condition than in the EuAA and PeAA conditions. Phosphorylation of ribosomal protein S6 [downstream of the mammalian target of Rapamycin complex 1 (mTORC1)] was significantly higher in the PoAA, but not PeAA, condition than in the EuAA condition. Conclusions: Portal, but not peripheral, AA delivery significantly enhanced hepatic protein synthesis under conditions in which AAs, glucose, insulin, and glucagon did not differ at the liver, an effect apparently mediated by mTORC1 signaling.",
author = "Dominique Dardevet and Kimball, {Scot R.} and Jefferson, {Leonard S.} and Cherrington, {Alan D.} and Didier R{\'e}mond and DiCostanzo, {Catherine A.} and Moore, {Mary Courtney}",
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Portal infusion of amino acids is more efficient than peripheral infusion in stimulating liver protein synthesis at the same hepatic amino acid load in dogs. / Dardevet, Dominique; Kimball, Scot R.; Jefferson, Leonard S.; Cherrington, Alan D.; Rémond, Didier; DiCostanzo, Catherine A.; Moore, Mary Courtney.

In: American Journal of Clinical Nutrition, Vol. 88, No. 4, 01.10.2008, p. 986-996.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Portal infusion of amino acids is more efficient than peripheral infusion in stimulating liver protein synthesis at the same hepatic amino acid load in dogs

AU - Dardevet, Dominique

AU - Kimball, Scot R.

AU - Jefferson, Leonard S.

AU - Cherrington, Alan D.

AU - Rémond, Didier

AU - DiCostanzo, Catherine A.

AU - Moore, Mary Courtney

PY - 2008/10/1

Y1 - 2008/10/1

N2 - Background: Hepatic glucose uptake is enhanced by the portal delivery of glucose, which creates a negative arterioportal substrate gradient. Hepatic amino acid (AA) utilization may be regulated by the same phenomenon, but this has not been proven. Objective: We aimed to assess hepatic AA balance and protein synthesis with or without a negative arterioportal AA gradient. Design: Somatostatin was infused intravenously, and insulin and glucagon were replaced intraportally at 4- and 3-fold basal rates, respectively, in 3 groups (n = 9 each) of conscious dogs with catheters for hepatic balance measurement. Arterial glucose concentrations were clamped at 9 mmol/L. An AA mixture was infused intravenously to maintain basal concentrations (EuAA), intraportally to mimic the postmeal AA increase (PoAA), or intravenously (PeAA) to match the hepatic AA load in PoAA. Protein synthesis was assessed with a primed, continuous [ 14C]leucine infusion. Results: Net hepatic glucose uptake in the PoAA condition was ≤50% of that in the EuAA and PeAA conditions (P < 0.05). In the PoAA and PeAA conditions, hepatic intracellular leucine concentrations were 2- to 2.5-fold those in the EuAA condition (P < 0.05); net hepatic leucine uptake and [14C]leucine utilization were ≈2-fold greater (P < 0.05) and albumin synthesis was 30% greater (P < 0.05) in the PoAA condition than in the EuAA and PeAA conditions. Phosphorylation of ribosomal protein S6 [downstream of the mammalian target of Rapamycin complex 1 (mTORC1)] was significantly higher in the PoAA, but not PeAA, condition than in the EuAA condition. Conclusions: Portal, but not peripheral, AA delivery significantly enhanced hepatic protein synthesis under conditions in which AAs, glucose, insulin, and glucagon did not differ at the liver, an effect apparently mediated by mTORC1 signaling.

AB - Background: Hepatic glucose uptake is enhanced by the portal delivery of glucose, which creates a negative arterioportal substrate gradient. Hepatic amino acid (AA) utilization may be regulated by the same phenomenon, but this has not been proven. Objective: We aimed to assess hepatic AA balance and protein synthesis with or without a negative arterioportal AA gradient. Design: Somatostatin was infused intravenously, and insulin and glucagon were replaced intraportally at 4- and 3-fold basal rates, respectively, in 3 groups (n = 9 each) of conscious dogs with catheters for hepatic balance measurement. Arterial glucose concentrations were clamped at 9 mmol/L. An AA mixture was infused intravenously to maintain basal concentrations (EuAA), intraportally to mimic the postmeal AA increase (PoAA), or intravenously (PeAA) to match the hepatic AA load in PoAA. Protein synthesis was assessed with a primed, continuous [ 14C]leucine infusion. Results: Net hepatic glucose uptake in the PoAA condition was ≤50% of that in the EuAA and PeAA conditions (P < 0.05). In the PoAA and PeAA conditions, hepatic intracellular leucine concentrations were 2- to 2.5-fold those in the EuAA condition (P < 0.05); net hepatic leucine uptake and [14C]leucine utilization were ≈2-fold greater (P < 0.05) and albumin synthesis was 30% greater (P < 0.05) in the PoAA condition than in the EuAA and PeAA conditions. Phosphorylation of ribosomal protein S6 [downstream of the mammalian target of Rapamycin complex 1 (mTORC1)] was significantly higher in the PoAA, but not PeAA, condition than in the EuAA condition. Conclusions: Portal, but not peripheral, AA delivery significantly enhanced hepatic protein synthesis under conditions in which AAs, glucose, insulin, and glucagon did not differ at the liver, an effect apparently mediated by mTORC1 signaling.

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