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Am J Physiol Endocrinol Metab 293: E1103-E1111, 2007. First published August 7, 2007; doi:10.1152/ajpendo.00613.2006
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Effects of fasting on insulin action and glucose kinetics in lean and obese men and women

Bryan C. Bergman, Marc-Andre Cornier, Tracy J. Horton, and Daniel H. Bessesen

University of Colorado Health Sciences Center, Aurora, Colorado

Submitted 15 November 2006 ; accepted in final form 3 August 2007

The development of insulin resistance in the obese individual could impair the ability to appropriately adjust metabolism to perturbations in energy balance. We investigated a 12- vs. 48-h fast on hepatic glucose production (Ra), peripheral glucose uptake (Rd), and skeletal muscle insulin signaling in lean and obese subjects. Healthy lean [n = 14; age = 28.0 ± 1.4 yr; body mass index (BMI) = 22.8 ± 0.42] and nondiabetic obese (n = 11; age = 34.6 ± 2.3 yr; BMI = 36.1 ± 1.5) subjects were studied following a 12- and 48-h fast during 2 h of rest and a 3-h 40 mU·m–2·min–1 hyperinsulinemic-euglycemic clamp (HEC). Basal glucose Ra decreased significantly from the 12- to 48-h fast (lean 1.96 ± 0.23 to 1.63 ± 0.15; obese 1.23 ± 0.07 to 1.07 ± 0.07 mg·kg–1·min–1; P = 0.004) and was equally suppressed during the HEC after both fasts. The increase in glucose Rd during the HEC after the 12-h fast was significantly decreased in lean and obese subjects after the 48-h fast (lean 9.03 ± 1.17 to 4.16 ± 0.34, obese 6.10 ± 0.77 to 3.56 ± 0.30 mg·kg FFM–1·min–1; P < 0.001). After the 12- but not the 48-h fast, insulin-stimulated AKT Ser473 phosphorylation was greater in lean than obese subjects. We conclude that 1) 48 h of fasting produces a marked decline in peripheral insulin action, while suppression of hepatic glucose production is maintained in lean and obese men and women; and 2) the magnitude of this decline is greater in lean vs. obese subjects.

starvation; insulin resistance; obesity



Address for reprint requests and other correspondence: B. C. Bergman, Division of Endocrinology, Diabetes, and Metabolism, Univ. of Colorado Health Sciences Center at Fitzsimons, PO Box 6511, MS 8106, Aurora, CO 80045 (e-mail: Bryan.Bergman{at}uchsc.edu)




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