Elevated basal PI 3-kinase activity and reduced insulin signaling in sucrose-induced hepatic insulin resistance
| Autor: | Jeffrey S. Thresher, Jione Kang, Michael J. Pagliassotti, Chin K. Sung, Michael E. Bizeau |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Sucrose medicine.medical_specialty Insulin Receptor Substrate Proteins Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment Protein Serine-Threonine Kinases Rats Sprague-Dawley Phosphatidylinositol 3-Kinases chemistry.chemical_compound Insulin resistance Proto-Oncogene Proteins Physiology (medical) Internal medicine medicine Animals Insulin Phosphorylation biology Intracellular Signaling Peptides and Proteins Glucose clamp technique Phosphoproteins medicine.disease Receptor Insulin Rats Isoenzymes Insulin receptor Endocrinology Liver chemistry Basal (medicine) Glucose Clamp Technique biology.protein Tyrosine Insulin Resistance Signal transduction Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 282:E170-E176 |
| ISSN: | 1522-1555 0193-1849 |
| DOI: | 10.1152/ajpendo.2002.282.1.e170 |
| Popis: | Sucrose feeding reduces the ability of insulin to suppress glucose production and hepatic gluconeogenesis. The present study examined the effect of a high-sucrose diet on early insulin-signaling steps in the liver. Rats were provided a high-starch (STD, control diet) or high-sucrose diet (HSD) for 3 wk. On the day of study, overnight-fasted rats were anesthetized and injected with either saline ( n = 5/diet group) or insulin (2 mU/kg, n = 5/diet group) via the portal vein. Portal venous blood and liver tissue were harvested 2 min after injections. Portal vein plasma glucose levels were not significantly different among groups, pooled average 147 ± 12 mg/dl. Western blot analysis revealed no significant differences in the amount of insulin receptor (IR), insulin receptor substrates-1 and -2 (IRS-1, IRS-2), and the p85 subunit of phosphatidylinositol (PI) 3-kinase. In contrast, the amount of the p110β subunit of PI 3-kinase was increased ∼2-fold in HSD vs. STD ( P < 0.05). After saline injection, tyrosine phosphorylation (pY) of IR, IRS-1, and IRS-2 was not significantly different between groups. However, PI 3-kinase activity associated with phosphorylated proteins was increased ∼40% in HSD vs. STD ( P < 0.05). After insulin injection, pY of the IR was not different between groups, whereas pY of IRS-1 and IRS-2 was reduced ( P < 0.05) in HSD vs. STD. In addition, association of IRS-1 and IRS-2 with p85 was significantly reduced in HSD vs. STD. These data demonstrate that an HSD impairs insulin-stimulated early postreceptor signaling (pY of IRS proteins, IRS interaction with p85). Furthermore, the increased amount of p110β and increased basal PI 3-kinase activity suggest a diet-induced compensatory response. |
| Databáze: | OpenAIRE |
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