Rosiglitazone Reduces Glucose-Stimulated Insulin Secretion Rate and Increases Insulin Clearance in Nondiabetic, Insulin-Resistant Individuals
- Sun H. Kim1,
- Fahim Abbasi1,
- James W. Chu1,
- Tracey L. McLaughlin1,
- Cindy Lamendola1,
- Kenneth S. Polonsky2 and
- Gerald M. Reaven1
- 1Department of Medicine, Stanford University School of Medicine, Stanford, California
- 2Department of Medicine, Washington University, St. Louis, Missouri
- Address correspondence and reprint requests to Gerald M. Reaven, MD, Division of Cardiovascular Medicine, Falk Cardiovascular Research Center, Stanford Medical Center, 300 Pasteur Dr., Stanford, CA 94305-5406. E-mail: greaven{at}cvmed.stanford.edu
Abstract
Compensatory hyperinsulinemia permitting insulin-resistant individuals to maintain normal glucose tolerance is associated with a left shift in the glucose-stimulated insulin secretion rate (GS-ISR) dose-response curve and decrease in the insulin metabolic clearance rate (I-MCR). To see whether these changes would reverse with improvement in insulin sensitivity, 14 nondiabetic insulin-resistant subjects received rosiglitazone for 12 weeks (4 mg daily for 4 weeks and then 8 mg daily for 8 weeks). Insulin-mediated glucose uptake was quantified by measuring the steady-state plasma glucose concentration during the insulin suppression test. GS-ISR and I-MCR were determined during a 240-min graded intravenous glucose infusion. I-MCR was also calculated during the insulin suppression test. After rosiglitazone treatment, insulin sensitivity improved with significant fall in steady-state plasma glucose (means ± SE from 13.5 ± 0.62 to 9.8 ± 1.02 mmol/l, P < 0.001). In response, the integrated GS-ISR decreased by 21% (P < 0.001), with a right shift in the dose-response curve. Calculated I-MCR increased by 34% (P = 0.008) during the insulin suppression test and by 21% (P = 0.03) during the graded glucose infusion. In conclusion, enhanced insulin sensitivity in rosiglitazone-treated nondiabetic insulin-resistant individuals was associated with a shift to the right in the GS-ISR dose-response curve and an increase in I-MCR.
- AUC, area under the curve
- FFA, free fatty acid
- GS-ISR, glucose-stimulated insulin secretion rate
- I-MCR, insulin metabolic clearance rate
- SSPG, steady-state plasma glucose
Footnotes
-
J.W.C., C.L., and G.M.R. have received consulting fees, honoraria, and grant/research support, respectively, from GlaxoSmithKline.
-
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
- Accepted April 21, 2005.
- Received October 8, 2004.
- DIABETES
