内科学
内分泌学
胰岛素抵抗
胰岛素
过剩4
葡萄糖摄取
胰岛素受体
骨骼肌
蛋白激酶B
葡萄糖转运蛋白
医学
碳水化合物代谢
脂肪组织
胰腺激素
葡萄糖钳夹技术
高胰岛素血症
生物
糖尿病
基础(医学)
肥胖
葡萄糖稳态
化学
磷酸化
生物化学
作者
Paola Ramos,Kelli A. Lytle,Danae A. Delivanis,Sören Nielsén,Nathan K. LeBrasseur,Michael D. Jensen
标识
DOI:10.1210/clinem/dgaa919
摘要
Skeletal muscle is the primary site for insulin-stimulated glucose disposal, and muscle insulin resistance is central to abnormal glucose metabolism in obesity. Whether muscle insulin signaling to the level of Akt/AS160 is intact in insulin-resistant obese humans is controversial.We defined a linear range of insulin-stimulated systemic and leg glucose uptake in 14 obese and 14 nonobese volunteers using a 2-step insulin clamp (Protocol 1) and then examined the obesity-related defects in muscle insulin action in 16 nonobese and 25 obese male and female volunteers matched for fitness using a 1-step, hyperinsulinemic, euglycemic clamp coupled with muscle biopsies (Protocol 2).Insulin-stimulated glucose disposal (Si) was reduced by > 60% (P < 0.0001) in the obese group in Protocol 2; however, the phosphorylation of Akt and its downstream effector AS160 were not different between nonobese and obese groups. The increase in phosphorylation of Akt2 in response to insulin was positively correlated with Si for both the nonobese (r = 0.53, P = 0.03) and the obese (r = 0.55, P = 0.01) groups. Total muscle GLUT4 protein was 17% less (P < 0.05) in obese subjects.We suggest that reduced muscle glucose uptake in obesity is not due to defects in the insulin signaling pathway at the level of Akt/AS160, which suggests there remain significant gaps in our knowledge of muscle insulin resistance in obesity. Our data imply that models of acute lipotoxicity do not replicate the pathophysiology of obesity.
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