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Comparative Study
. 2012 Nov 15;303(10):E1202-11.
doi: 10.1152/ajpendo.00140.2012. Epub 2012 Sep 25.

Portal glucose delivery stimulates muscle but not liver protein metabolism

Guillaume Kraft  1 , Katie C Coate, Dominique Dardevet, Ben Farmer, E Patrick Donahue, Phillip E Williams, Alan D Cherrington, Mary Courtney Moore
Affiliations
Comparative Study

Portal glucose delivery stimulates muscle but not liver protein metabolism

Guillaume Kraft et al. Am J Physiol Endocrinol Metab. .

Abstract

Portal vein glucose delivery (the portal glucose signal) stimulates glucose uptake and glycogen storage by the liver, whereas portal amino acid (AA) delivery (the portal AA signal) induces an increase in protein synthesis by the liver. During a meal, both signals coexist and may interact. In this study, we compared the protein synthesis rates in the liver and muscle in response to portal or peripheral glucose infusion during intraportal infusion of a complete AA mixture. Dogs were surgically prepared with hepatic sampling catheters and flow probes. After a 42-h fast, they underwent a 3-h hyperinsulinemic (4× basal) hyperglucagonemic (3× basal) hyperglycemic (≈160 mg/dl) hyperaminoacidemic (hepatic load 1.5× basal; delivered intraportally) clamp (postprandial conditions). Glucose was infused either via a peripheral (PeG; n = 7) or the portal vein (PoG; n = 8). Protein synthesis was assessed with a primed, continuous [(14)C]leucine infusion. Net hepatic glucose uptake was stimulated by portal glucose infusion (+1 mg·kg(-1)·min(-1), P < 0.05) as expected, but hepatic fractional AA extraction and hepatic protein synthesis did not differ between groups. There was a lower arterial AA concentration in the PoG group (-19%, P < 0.05) and a significant stimulation (+30%) of muscle protein synthesis associated with increased expression of LAT1 and ASCT2 AA transporters and p70S6 phosphorylation. Concomitant portal glucose and AA delivery enhances skeletal muscle protein synthesis compared with peripheral glucose and portal AA delivery. These data suggest that enteral nutrition support may have an advantage over parenteral nutrition in stimulating muscle protein synthesis.

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Figures

Fig. 1.
Fig. 1.
Hormone concentrations during the basal and experimental periods in conscious, 42-h-fasted dogs during a pancreatic clamp with portal infusion of hormones and either peripheral [peripheral glucose delivery group (PeG); n = 7] or portal infusion of glucose [portal glucose delivery group (PoG); n = 8]. There were no significant differences between groups.
Fig. 2.
Fig. 2.
Arterial blood glucose (A), arterioportal glucose (A-P) gradient (B), net hepatic glucose balance (C), and nonhepatic glucose balance (D) during basal and experimental periods in conscious, 42-h-fasted dogs given peripheral (PeG; n = 7) or portal glucose (PoG; n = 8) infusion with simultaneous amino acid infusion. The statistical evaluation of the data was performed by analysis of variance to test the group and the time effects. **Post hoc differences between groups were considered significant when P < 0.05.
Fig. 3.
Fig. 3.
Arterial leucine-specific activity (in dpm/nmol) in dogs during a primed (6.8 mCi/kg) continuous infusion (0.21 mCi·kg−1·min−1) of [14C]leucine starting at 120 min. The 2 groups of dogs were studied during hyperaminoacidemia via portal infusion of amino acids and received glucose via either a peripheral vein (PeG group; n = 7) or the portal vein (PoG group; n = 8).
Fig. 4.
Fig. 4.
Hepatic constitutive (A) and muscle protein synthesis rates (C) associated with relative phosphorylation of AMP-activated protein kinase (AMPK), mammalian _target of rapamycin (mTOR), Akt, eukaryotic initiation factor 4E-binding protein-1 (4E-BP1), and p70S6 in the liver (B) and muscle (D) and mRNA content of SLC38A2, SLC7A5, and SLC1A5 [or system A transport of amino acid (SNAT2), system L amino acid transporter 1 (LAT1), and system ASC amino acid transporter 2 (ASCT2), 3 types of amino acid transport systems] and caspase-3 (CASP3) and m-calpain (CAPN2) (2 types of proteolytic systems) in the muscle (E). Tissues were taken from dogs at the end of a 3-h pancreatic clamp with portal amino acid infusion and either peripheral (PeG; n = 7) or portal infusion of glucose (PoG; n = 8). **Differences were considered significant when P < 0.05.
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