Bergman Bryan C, Cornier Marc-Andre, Horton Tracy J, Bessesen Daniel H
Division of Endocrinology, Diabetes, and Metabolism, Univ. of Colorado Health Sciences Center at Fitzsimons, PO Box 6511, MS 8106, Aurora, CO 80045, USA.
Am J Physiol Endocrinol Metab. 2007 Oct;293(4):E1103-11. doi: 10.1152/ajpendo.00613.2006. Epub 2007 Aug 7.
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 (R(a)), peripheral glucose uptake (R(d)), 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 mUxm(-2)xmin(-1) hyperinsulinemic-euglycemic clamp (HEC). Basal glucose R(a) 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 mgxkg(-1)xmin(-1); P = 0.004) and was equally suppressed during the HEC after both fasts. The increase in glucose R(d) 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 mgxkg FFM(-1)xmin(-1); P < 0.001). After the 12- but not the 48-h fast, insulin-stimulated AKT Ser(473) 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.
肥胖个体中胰岛素抵抗的发展可能会损害其根据能量平衡的扰动适当调节新陈代谢的能力。我们研究了12小时禁食与48小时禁食对瘦人和肥胖受试者肝脏葡萄糖生成（R(a)）、外周葡萄糖摄取（R(d)）以及骨骼肌胰岛素信号传导的影响。健康瘦人[n = 14；年龄 = 28.0 ± 1.4岁；体重指数（BMI） = 22.8 ± 0.42]和非糖尿病肥胖者（n = 11；年龄 = 34.6 ± 2.3岁；BMI = 36.1 ± 1.5）在禁食12小时和48小时后，进行2小时休息以及3小时40 mU·m(-2)·min(-1)的高胰岛素-正常血糖钳夹试验（HEC）。基础葡萄糖R(a)在禁食12小时至48小时期间显著下降（瘦人从1.96 ± 0.23降至1.63 ± 0.15；肥胖者从1.23 ± 0.07降至1.07 ± 0.07 mg·kg(-1)·min(-1)；P = 0.004），并且在两次禁食后的HEC期间均受到同等程度的抑制。在禁食48小时后，瘦人和肥胖受试者在禁食12小时后HEC期间葡萄糖R(d)的增加显著降低（瘦人从9.03 ± 1.17降至4.16 ± 0.34，肥胖者从6.10 ± 0.77降至3.56 ± 0.30 mg·kg去脂体重(-1)·min(-1)；P < 0.001）。在禁食12小时而非48小时后，胰岛素刺激的AKT Ser(473)磷酸化在瘦人比肥胖受试者中更高。我们得出结论：1）48小时禁食会导致外周胰岛素作用显著下降，而肝脏葡萄糖生成的抑制在瘦人和肥胖男性及女性中均得以维持；2）这种下降的幅度在瘦人比肥胖受试者中更大。
