title: Impairment of cardiac insulin signaling in fructose-fed ovariectomized female Wistar rats.
abstract: BACKGROUND
  Fructose consumption produces deleterious metabolic effects in animal models. The sites of fructose-induced insulin resistance are documented to be the liver, skeletal muscle, and adipose tissue, but effects of fructose-rich diet on cardiac insulin signaling and action were not investigated.
  
  
  OBJECTIVE
  In order to study the potential fructose effects on development of cardiac insulin resistance, we analyzed biochemical parameters relevant for insulin action and phosphorylation of insulin signaling molecules, plasma membrane glucose transporter type 4 (GLUT4) content, and phosphorylation of endothelial nitric oxide synthase (eNOS), in ovariectomized female rats on fructose-enriched diet, in basal and insulin-stimulated conditions.
  
  
  RESULTS
  Fructose-fed rats (FFR) had increased content of visceral adipose tissue, but not body weight. Food intake was decreased, while fluid and caloric intake were increased in FFR. Additionally, fructose diet increased plasma insulin, blood triglycerides level, and HOMA index. Stimulation of protein kinase B (Akt) signaling pathway by insulin was reduced in rats on fructose-enriched diet, but effect of fructose on extracellular signal-regulated kinase (Erk 1/2) phosphorylation was not observed. Furthermore, insulin-induced GLUT4 presence in plasma membranes of cardiac cells was decreased by fructose diet, as well as insulin stimulation of eNOS phosphorylation at Ser(1177).
  
  
  CONCLUSIONS
  In summary, these results strongly support our hypothesis that fructose diet-induced changes of plasma lipid profile and insulin sensitivity are accompanied with decrease in cardiac insulin action in ovariectomized female rats.
authors.affiliation: Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, P.O. Box 522, 11001, Belgrade, Serbia. zzakula@vinca.rs
authors.forename: Zorica
authors.initials: Z
authors.lastname: Zakula
authors.forename: Goran
authors.initials: G
authors.lastname: Koricanac
authors.forename: Snezana
authors.initials: S
authors.lastname: Tepavcevic
authors.forename: Mojca
authors.initials: M
authors.lastname: Stojiljkovic
authors.forename: Tijana
authors.initials: T
authors.lastname: Milosavljevic
authors.forename: Esma R
authors.initials: ER
authors.lastname: Isenovic
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005632:Fructose / Q000008:administration & dosage*; D051275:Glucose Transporter Type 4 / Q000097:blood; D006321:Heart / Q000187:drug effects*; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010052:Ovariectomy; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D014280:Triglycerides / Q000097:blood
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; C495694:Slc2a4 protein, rat; D014280:Triglycerides; D005632:Fructose; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases