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Free Fatty Acid-Induced Hepatic Insulin Resistance is Attenuated Following Lifestyle Intervention in Obese Individuals with Impaired Glucose Tolerance

Haus, M., Jacob ; Solomon, P. J., Thomas ; Marchetti, M., Christine ; Edmison, M., John ; González, P., Frank ; Kirwan, P., John

The Journal of Clinical Endocrinology & Metabolism, 2010, Vol.95(1), pp.323-327 [Tạp chí có phản biện]

ISSN: 0021-972X

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  • Nhan đề:
    Free Fatty Acid-Induced Hepatic Insulin Resistance is Attenuated Following Lifestyle Intervention in Obese Individuals with Impaired Glucose Tolerance
  • Tác giả: Haus, M., Jacob ; Solomon, P. J., Thomas ; Marchetti, M., Christine ; Edmison, M., John ; González, P., Frank ; Kirwan, P., John
  • Chủ đề: Medicine
  • Là 1 phần của: The Journal of Clinical Endocrinology & Metabolism, 2010, Vol.95(1), pp.323-327
  • Mô tả: OBJECTIVE:: The objective of the study was to examine the effects of an exercise/diet lifestyle intervention on free fatty acid (FFA)-induced hepatic insulin resistance in obese humans. RESEARCH DESIGN AND METHODS:: Obese men and women (n = 23) with impaired glucose tolerance were randomly assigned to either exercise training with a eucaloric (EU; ∼1800 kcal; n = 11) or hypocaloric (HYPO; ∼1300 kcal; n = 12) diet for 12 wk. Hepatic glucose production (HGP; milligrams per kilogram fat-free mass per minute) and hepatic insulin resistance were determined using a two-stage sequential hyperinsulinemic (40 mU/m · min) euglycemic (5.0 mm) clamp with [3-H]glucose. Measures were obtained at basal, during insulin infusion (INS; 120 min), and insulin plus intralipid/heparin infusion (INS/FFA; 300 min). RESULTS:: At baseline, basal HGP was similar between groups; hyperinsulinemia alone did not completely suppress HGP, whereas INS/FFA exhibited less suppression than INS (EU, 4.6 ± 0.8, 2.0 ± 0.5, and 2.6 ± 0.4; HYPO, 3.8 ± 0.5, 1.2 ± 0.3, and 2.3 ± 0.4, respectively). After the intervention the HYPO group lost more body weight (P < 0.05) and fat mass (P < 0.05). However, both lifestyle interventions reduced hepatic insulin resistance during basal (P = 0.005) and INS (P = 0.001) conditions, and insulin-mediated suppression of HGP during INS was equally improved in both groups (EU: −42 ± 22%; HYPO: −50 ± 20%, before vs. after, P = 0.02). In contrast, the ability of insulin to overcome FFA-induced hepatic insulin resistance and HGP was improved only in the HYPO group (EU: −15 ± 24% vs. HYPO: −58 ± 19%, P = 0.02). CONCLUSIONS:: Both lifestyle interventions are effective in reducing hepatic insulin resistance under basal and hyperinsulinemic conditions. However, the reversal of FFA-induced hepatic insulin resistance is best achieved with a combined exercise/caloric-restriction intervention.
  • Số nhận dạng: ISSN: 0021-972X

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