title: Glucose and fructose have sugar-specific effects in both liver and skeletal muscle in vivo: a role for liver fructokinase.
abstract: We examined glucose and fructose effects on serine phosphorylation levels of a range of proteins in rat liver and muscle cells. For this, healthy adult rats were subjected to either oral glucose or fructose loads. A mini-array system was utilized to determine serine phosphorylation levels of liver and skeletal muscle proteins. A glucose oral load of 125 mg/100 g body weight (G 1/2) did not induce changes in phosphorylated serines of the proteins studied. Loading with 250 mg/100 g body weight of fructose (Fr), which induced similar glycemia levels as G 1/2, significantly increased serine phosphorylation of liver cyclin D3, PI3 kinase/p85, ERK-2, PTP2 and clusterin. The G 1/2 increased serine levels of the skeletal muscle proteins cyclin H, Cdk2, IRAK, total PKC, PTP1B, c-Raf 1, Ras and the β-subunit of the insulin receptor. The Fr induced a significant increase only in muscle serine phosphorylation of PI3 kinase/p85. The incubation of isolated rat hepatocytes with 10 mM glucose for 5 min significantly increased serine phosphorylation of 31 proteins. In contrast, incubation with 10 mM fructose produced less intense effects. Incubation with 10 mM glucose plus 75 µM fructose counteracted the effects of the incubation with glucose alone, except those on Raf-1 and Ras. Less marked effects were detected in cultured muscle cells incubated with 10 mM glucose or 10 mM glucose plus 75 µM fructose. Our results suggest that glucose and fructose act as specific functional modulators through a general mechanism that involves liver-generated signals, like micromolar fructosemia, which would inform peripheral tissues of the presence of either glucose- or fructose-derived metabolites.
authors.affiliation: Dept. Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Fernández-Novell
authors.affiliation: Dept. Animal Medicine and Surgery, Autonomous University of Barcelona, Bellaterra, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Ramió-Lluch
authors.affiliation: Dept. Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Orozco
authors.affiliation: Dept. Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Gómez-Foix
authors.affiliation: Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; Institute for Research in Biomedicine, Barcelona Science Park, Barcelona, Spain.
authors.forename: Joan J
authors.initials: JJ
authors.lastname: Guinovart
authors.affiliation: Dept. Animal Medicine and Surgery, Autonomous University of Barcelona, Bellaterra, Spain.
authors.forename: Joan E
authors.initials: JE
authors.lastname: Rodríguez-Gil
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D051152:Clusterin / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D005631:Fructokinases / Q000378:metabolism*; D005632:Fructose / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: D051152:Clusterin; D016213:Cyclins; D005632:Fructose; D012694:Serine; D005631:Fructokinases; D019869:Phosphatidylinositol 3-Kinases; C046173:fructokinase; D053592:Interleukin-1 Receptor-Associated Kinases; D019908:Proto-Oncogene Proteins c-raf; D019950:Mitogen-Activated Protein Kinase 1; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516610:Ptpn1 protein, rat; D018631:ras Proteins; D005947:Glucose