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Thiazolidinedione treatment prevents free fatty acid-induced insulin resistance in male wistar ratsHevener, Andrea ...We sought to ascertain whether pretreatment with troglitazone (20 days) could prevent acute free fatty acid (FFA)-induced insulin resistance in male Wistar rats. Animals were divided into three ... groups: 1) control, 2) FFA infusion alone (FFA1), and 3) thiazolidinedione (TZD)-treated + FFA infusion (FFA1). Days before a hyperinsulinemic-euglycemic clamp, all animals were cannulated in the jugular vein (infusion) and carotid artery (sampling). Animals were allowed 5 days to recover from surgery and fasted 12 h before the experiment. Glucose (variable), insulin (40 mU. kg(-1). min(-1)), and Liposyn (heparinized10% lipid emulsion) infusions were initiated simultaneously and continued from 0-120 min. Steady-state glucose, 8.3 +/- 0.14 mmol/l, and insulin concentrations, 7.3 +/- 2.45 nmol/l, were the same between groups. Interestingly, steady-state FFA levels were significantly lower in animals pretreated with TZD compared with FFA alone (1.83 +/- 0.26 vs. 2.96 +/- 0.25 mmol/l; P = 0.009), despite matched intralipid infusion rates. A second group of TZD-treated animals (TZD + FFA2) were infused with intralipid at a higher infusion rate (44%) to match the arterial concentrations of FFA1. The glucose infusion and insulin-stimulated glucose disposal rates (GDRs) were significantly decreased (40%) for untreated Liposyn infused (FFA1) compared with control rats. In addition, insulin receptor substrate-1 (IRS-1) phosphorylation and IRS-1-associated phosphatidylinositol (PI) 3-kinase activity was significantly reduced, 30-50%, in FFA1 rats. TZD pretreatment prevented the FFA-induced decrement in insulin signaling. Fatty acid translocase (FAT/CD36) also was significantly reduced (56%) in untreated FFA1 rats after the clamp but remained identical to control values for TZD-treated rats. In conclusion, acutely elevated FFA levels1) induced a significant reduction in tracer-determined GDR paralleled by impaired tyrosine phosphorylation of IRS-1(Abstract truncatedVir: Diabetes. - ISSN 0012-1797 (Letn. 50, št. 10, 2001, str. 2316-2322)Vrsta gradiva - članek, sestavni delLeto - 2001Jezik - angleškiCOBISS.SI-ID - 17425113
Avtor
Hevener, Andrea |
Reichart, Donna |
Janež, Andrej, 1971- |
Olefsky, Jerrold M.
Teme
Insulin Resistance |
Chromans |
Pharmacology |
Fatty Acids, Nonesterified |
Liver |
Metabolism |
Drug Effects |
Thiazoles |
Pharmacology |
Fat Emulsions, Intravenous |
Pharmacology |
Glucose |
Metabolism |
Insulin |
Pharmacology |
Phosphatidylinositols |
Ligands |
Membrane Glycoproteins |
Antagonists And Inhibitors |
Muscle, Skeletal |
Drug Effects |
Phosphoproteins |
Metabolism |
Phosphorylation |
Drug Effects |
Rats, Wistar |
Receptors, Cytoplasmic And Nuclear |
Agonists |
Transcription Factors |
Tyrosine |
Metabolism |
Insulinska rezistenca |
Jetra |
Kromani |
Maščobne kisline neesterificirane |
Tiazoli |
Fosfatidilinozitoli |
Fosfoproteini |
Fosforilacija |
Glukoza |
Inzulin |
Ligandi |
Maščobne emulzije intravenske |
Membranski glikoproteini |
Mišica skeletna |
Podgane, Wistar |
Receptorji, citoplazemski in jedrni |
Tirozin |
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Hevener, Andrea | ![]() |
Reichart, Donna | ![]() |
Janež, Andrej, 1971- | 18372 |
Olefsky, Jerrold M. | ![]() |
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