5-amino-imidazole carboxamide riboside increases glucose transport and cell-surface GLUT4 content in skeletal muscle from subjects with type 2 diabetes
5-amino-imidazole carboxamide riboside increases glucose transport and cell-surface GLUT4 content in skeletal muscle from subjects with type 2 diabetes
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DOI：
10.2337/diabetes.52.5.1066
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发表时间：
2003-05-01
期刊：
影响因子：
7.7
通讯作者：
Wallberg-Henriksson, H
中科院分区：
文献类型：
--
作者：
Koistinen, HA;Galuska, D;Wallberg-Henriksson, H
AMP-activated protein kinase（AMPK）activation by AICAR.（5-andno-咪唑甲酰胺核苷）与啮齿动物骨骼肌中通过胰岛素非依赖性途径增加的葡萄糖转运相关。我们确定了胰岛素和/或AICAR暴露对非糖尿病男性和2型糖尿病男性骨骼肌葡萄糖转运和细胞表面GLUT 4含量的体外影响。AICAR在健康受试者中以剂量依赖性方式增加葡萄糖转运。胰岛素和AICAR增加葡萄糖转运和细胞表面GLUT 4含量在对照组中达到相似的程度。与此相反，胰岛素和AICAR刺激的葡萄糖转运和细胞表面GLUT 4含量的反应在2型糖尿病患者中受损。重要的是，2型糖尿病骨骼肌暴露于胰岛素和AICAR的组合增加了葡萄糖转运和细胞表面GLUT 4含量，达到对照组的水平。AICAR增加AMPK和乙酰辅酶A羧化酶磷酸化的程度相似，在骨骼肌受试者与2型糖尿病和非糖尿病受试者。我们的研究强调了AMPK依赖性途径在胰岛素抵抗骨骼肌中调节GLUT 4和葡萄糖转运活性的潜在重要性。AMPK的激活是通过增加胰岛素抵抗骨骼肌中细胞表面GLUT 4含量来增强葡萄糖转运的有吸引力的策略。
AMP-activated protein kinase (AMPK) activation by AICAR. (5-andno-imidazole carboxamide riboside) is correlated with increased glucose transport in rodent skeletal muscle via an insulin-independent pathway. We determined in vitro effects of insulin and/or AICAR exposure on glucose transport and cell-surface GLUT4 content in skeletal muscle from nondiabetic men and men with type 2 diabetes. AICAR increased glucose transport in a dose-dependent manner in healthy subjects. Insulin and AICAR increased glucose transport and cell-surface GLUT4 content to a similar extent in control subjects. In contrast, insulin- and AICAR-stimulated responses on glucose transport and cell-surface GLUT4 content were impaired in subjects with type 2 diabetes. Importantly, exposure of type 2 diabetic skeletal muscle to a combination of insulin and AICAR increased glucose transport and cell-surface GLUT4 content to levels achieved in control subjects. AICAR increased AMPK and acetyl-CoA carboxylase phosphorylation to a similar extent in skeletal muscle from subjects with type 2 diabetes and nondiabetic subjects. Our studies highlight the potential importance of AMPK-dependent pathways in the regulation of GLUT4 and glucose transport activity,in insulin-resistant skeletal muscle. Activation of AMPK is an attractive strategy to enhance glucose transport through increased cell surface GLUT4 content in insulin-resistant skeletal muscle.