title: Hepatic glucose uptake and disposition during short-term high-fat vs. high-fructose feeding.
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.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Katie C
authors.initials: KC
authors.lastname: Coate
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Guillaume
authors.initials: G
authors.lastname: Kraft
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee; genie.moore@vanderbilt.edu.
authors.forename: Mary Courtney
authors.initials: MC
authors.lastname: Moore
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Marta S
authors.initials: MS
authors.lastname: Smith
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Christopher
authors.initials: C
authors.lastname: Ramnanan
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana;
authors.forename: Jose M
authors.initials: JM
authors.lastname: Irimia
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana;
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Roach
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Ben
authors.initials: B
authors.lastname: Farmer
authors.affiliation: 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.
authors.forename: Doss W
authors.initials: DW
authors.lastname: Neal
authors.affiliation: Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee; and Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Phil
authors.initials: P
authors.lastname: Williams
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Alan D
authors.initials: AD
authors.lastname: Cherrington
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D059305:Diet, High-Fat / Q000662:veterinary; D004040:Dietary Carbohydrates / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology*; D004285:Dogs; D005632:Fructose / Q000494:pharmacology*; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D014280:Triglycerides; D005632:Fructose; D019344:Lactic Acid; D005941:Glucokinase; D005947:Glucose; D005990:Glycerol
keywords: Glucokinase; glycogen; glycogen phosphorylase; glycogen synthase; insulin signaling