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Am J Physiol Endocrinol Metab. 2014 Jul 15;307(2):E151-60. doi: 10.1152/ajpendo.00083.2014. Epub 2014 May 27.

Hepatic glucose uptake and disposition during short-term high-fat vs. high-fructose feeding.

Author information

1
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee;
2
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee; genie.moore@vanderbilt.edu.
3
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana;
4
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee; Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee; and.
5
Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee; and Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee.

Abstract

In dogs consuming a high-fat and -fructose diet (52 and 17% of total energy, respectively) for 4 wk, hepatic glucose uptake (HGU) in response to hyperinsulinemia, hyperglycemia, and portal glucose delivery is markedly blunted with reduction in glucokinase (GK) protein and glycogen synthase (GS) activity. The present study compared the impact of selective increases in dietary fat and fructose on liver glucose metabolism. Dogs consumed weight-maintaining chow (CTR) or hypercaloric high-fat (HFA) or high-fructose (HFR) diets diet for 4 wk before undergoing clamp studies with infusion of somatostatin and intraportal insulin (3-4 times basal) and glucagon (basal). The hepatic glucose load (HGL) was doubled during the clamp using peripheral vein (Pe) glucose infusion in the first 90 min (P1) and portal vein (4 mg·kg(-1)·min(-1)) plus Pe glucose infusion during the final 90 min (P2). During P2, HGU was 2.8 ± 0.2, 1.0 ± 0.2, and 0.8 ± 0.2 mg·kg(-1)·min(-1) in CTR, HFA, and HFR, respectively (P < 0.05 for HFA and HFR vs. CTR). Compared with CTR, hepatic GK protein and catalytic activity were reduced (P < 0.05) 35 and 56%, respectively, in HFA, and 53 and 74%, respectively, in HFR. Liver glycogen concentrations were 20 and 38% lower in HFA and HFR than CTR (P < 0.05). Hepatic Akt phosphorylation was decreased (P < 0.05) in HFA (21%) but not HFR. Thus, HFR impaired hepatic GK and glycogen more than HFA, whereas HFA reduced insulin signaling more than HFR. HFA and HFR effects were not additive, suggesting that they act via the same mechanism or their effects converge at a saturable step.

KEYWORDS:

Glucokinase; glycogen; glycogen phosphorylase; glycogen synthase; insulin signaling

PMID:
24865981
PMCID:
PMC4101635
DOI:
10.1152/ajpendo.00083.2014
[Indexed for MEDLINE]
Free PMC Article
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