PMID- 10827205 OWN - NLM STAT- MEDLINE DCOM- 20000623 LR - 20220409 IS - 0022-3166 (Print) IS - 0022-3166 (Linking) VI - 130 IP - 6 DP - 2000 Jun TI - A high fructose diet affects the early steps of insulin action in muscle and liver of rats. PG - 1531-5 AB - A high fructose diet induces insulin resistance in rats, although the exact molecular mechanism involved is unknown. In this study, we used immunoprecipitation and immunoblotting to examine the levels and phosphorylation status of the insulin receptor (IR) and insulin receptor substrate-1 (IRS-1), as well as the association of the IRS-1 with phosphatidylinositol 3-kinase (PI 3-kinase), and phosphotyrosine phosphatase (SHP2) in the liver and muscle of rats fed a control or high fructose diet for 28 d. There were no differences in IR and the IRS-1 protein levels in the liver and muscle of rats fed the control and high fructose diets. However, tyrosine-phosphorylation of the insulin receptor after insulin stimulation was reduced to 71 +/- 2% (P < 0.05) of control in the liver of the fructose-fed rats. In samples previously immunoprecipitated with anti-IRS-1 antibody and blotted with antiphosphotyrosine antibody, the insulin-stimulated IRS-1 phosphorylation levels in the liver and muscle of the fructose-fed group were only 70 +/- 6% (P < 0.05) and 76 +/- 5% (P < 0.05) of those of control rats, respectively. The insulin-stimulated IRS-1 association with PI 3-kinase was reduced to 84 +/- 3% (P < 0.05) in the liver and to 84 +/- 4% (P < 0.05) in the muscle of the fructose-fed group compared with control rats. Insulin-stimulated IRS-1 association with SHP2 was reduced to 79 +/- 5% (P < 0.05) in liver of the fructose-fed rats. These data suggest that changes in the early steps of insulin signal transduction may have an important role in the insulin resistance observed in these rats. FAU - Bezerra, R M AU - Bezerra RM AD - Departamento de Planejamento Alimentar e Nutricao, Faculdade de Engenharia de Alimentos and Departamento de Clinica Medica, Faculdade de Ciencias Medicas, Universidade Estadual de Campinas, Campinas, SP, Brasil. FAU - Ueno, M AU - Ueno M FAU - Silva, M S AU - Silva MS FAU - Tavares, D Q AU - Tavares DQ FAU - Carvalho, C R AU - Carvalho CR FAU - Saad, M J AU - Saad MJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Nutr JT - The Journal of nutrition JID - 0404243 RN - 0 (Blood Glucose) RN - 0 (Dietary Carbohydrates) RN - 0 (Insulin) RN - 0 (Insulin Receptor Substrate Proteins) RN - 0 (Irs1 protein, rat) RN - 0 (Phosphoproteins) RN - 30237-26-4 (Fructose) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.10.1 (Receptor, Insulin) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatases) SB - IM MH - Animals MH - Blood Glucose/drug effects MH - Body Weight/drug effects MH - Dietary Carbohydrates/administration & dosage/*pharmacology MH - Fructose/administration & dosage/*pharmacology MH - Insulin/*metabolism MH - Insulin Receptor Substrate Proteins MH - Liver/*drug effects/enzymology/metabolism MH - Male MH - Muscle, Skeletal/*drug effects/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphoproteins/drug effects/metabolism MH - Phosphorylation/drug effects MH - Protein Tyrosine Phosphatases/metabolism MH - Rats MH - Rats, Wistar MH - Receptor, Insulin/*drug effects/metabolism EDAT- 2000/05/29 09:00 MHDA- 2000/07/06 11:00 CRDT- 2000/05/29 09:00 PHST- 2000/05/29 09:00 [pubmed] PHST- 2000/07/06 11:00 [medline] PHST- 2000/05/29 09:00 [entrez] AID - 10.1093/jn/130.6.1531 [doi] PST - ppublish SO - J Nutr. 2000 Jun;130(6):1531-5. doi: 10.1093/jn/130.6.1531.