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Submitted on February 2, 2005
Accepted on June 16, 2005
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo and Kaleida Health, 3 Gates Circle, Buffalo, NY 14209
* To whom correspondence should be addressed. E-mail: pdandona{at}KaleidaHealth.org.
Objective: Elevation of free fatty acids (FFA) by the infusion of triglyceride-heparin emulsion infusion(TG-Hep) causes insulin resistance(IR). We examined the effect of insulin sensitizer(rosiglitazone) on FFA induced IR.
Design: 9 obese subjects underwent a 6-hour infusion of TG-Hep before and after 6 weeks of rosiglitazone(8 mg/day) treatment. Hyperinsulinemic euglycemic clamps were performed during 0-2 h and 4-6 h of TG-Hep.
Results: Following rosiglitazone for 6 weeks, fasting FFA concentration fell, but not significantly (489 ± 63 at 0w; 397 ± 58 µmol/L at 6w; P = 0.16), while C-reactive protein(CRP)(4.26 ± 0.95 at 0w; 2.03 ± 0.45 µg/mL at 6w) and Serum Amyloid A(SAA)(17.36 ± 4.63 at 0w; 8.77 ± 1.63 µg/mL at 6w) decreased significantly. At 0w, TG-Hep infusion caused a decrease in glucose infusion rate (GIR) from 4.49 ± 0.95 mg/kg/min to 3.02 ± 0.59 mg/kg/min(P = 0.018). Rosiglitazone treatment resulted in an increase in baseline GIR to 6.29 ± 0.81 mg/kg/min(P = 0.03 vs. 0wk), which decreased to 4.52 ± 0.53 mg/kg/min (P = 0.001) after 6 h of TG-Hep infusion. The decrease in glucose infusion rate(GIR) induced by TG-Hep infusion was similar before and after rosiglitazone therapy (1.47 ± 0.50 vs. 1.77 0.3 mg/kg/min,[or 28.9 ± 6.5% vs. 26.4 ± 3.7%], P = 0.51). The rise in FFA and triglycerides after TG-Hep infusion was significantly lower at 6 weeks(P = 0.006 for FFA, P = 0.024 for triglycerides).
Conclusions: We conclude that rosiglitazone 1) causes a significant increase in GIR; 2) induces a decrease in inflammatory mediators, CRP and SAA; 3)decreases the rise in FFA and TG following TG-Hep infusion; and 4)does not prevent FFA induced IR.
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