title: Fructose-induced stress signaling in the liver involves methylglyoxal.
abstract: BACKGROUND
  Fructose produces hepatic insulin resistance in humans and animals. We have proposed that the selective metabolism of fructose by the liver can, under conditions of elevated fructose delivery, inflict a metabolic insult that is localized to the hepatocyte. The present study was designed to identify potential cellular effectors of this insult.
  
  
  METHODS
  Primary hepatocytes were incubated with 8 mM glucose and 0.12% inulin (G, n = 6) or 8 mM glucose, 0.12% inulin and 28 mU of inulinase (GF, n = 6) in the presence or absence of insulin for 0, 2, or 4 h.
  
  
  RESULTS
  GF produced fructose concentrations of ~0.7 mM over the 4 h experiment. GF induced phosphorylation of MKK7 and JNK, phosphorylation of serine307 on IRS-1, and reduced tyrosine phosphorylation of IRS-1 and -2. GF increased ceramide levels and reactive oxygen species (ROS); however inhibitors of ceramide synthesis or ROS accumulation did not prevent GF-mediated changes in MKK7, JNK or IRS proteins. GF increased cellular methylglyoxal concentrations and a selective increase in methylglyoxal recapitulated the GF-induced changes in MKK7, JNK and IRS proteins.
  
  
  CONCLUSIONS
  We hypothesize that GF-mediated changes in stress signaling involve methylglyoxal in primary hepatocytes.
authors.affiliation: Department of Food Science and Human Nutrition, Colorado State University, 234 Gifford, Fort Collins, CO 80523-1571, USA.
authors.forename: Yuren
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Food Science and Human Nutrition, Colorado State University, 234 Gifford, Fort Collins, CO 80523-1571, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Food Science and Human Nutrition, Colorado State University, 234 Gifford, Fort Collins, CO 80523-1571, USA.
authors.forename: Gretchen
authors.initials: G
authors.lastname: Moran
authors.affiliation: Department of Food Science and Human Nutrition, Colorado State University, 234 Gifford, Fort Collins, CO 80523-1571, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Estrada
authors.affiliation: Department of Food Science and Human Nutrition, Colorado State University, 234 Gifford, Fort Collins, CO 80523-1571, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pagliassotti
keywords: Insulin resistance; Mitogen-activated protein kinase; Sucrose