Chronic Treatment With 5-Aminoimidazole-4-Carboxamide-1- -D-Ribofuranoside Increases Insulin-Stimulated Glucose Uptake and GLUT4 Translocation in Rat Skeletal Muscles in a Fiber Type--Specific Manner

作者：Esben Selmer Buhl, Niels Jessen, Ole Schmitz, Steen B. Pedersen, Oluf Borbye Pedersen, Geoffrey David Holman, Sten A. Lund · 发表于：Diabetes · 年份：2001 · DOI：10.2337/diabetes.50.1.12 · 被引用次数：184 · 研究领域：Metabolism, Diabetes, and Cancer、Pancreatic function and diabetes、Glycogen Storage Diseases and Myoclonus

Recent studies have demonstrated that chronic administration of AICAR (5-aminoimidazole-4-carboxamide- 1-beta-D-ribofuranoside), an activator of the AMP-activated protein kinase, increases hexokinase activity and the contents of total GLUT4 and glycogen in rat skeletal muscles. To explore whether AICAR also affects insulin-stimulated glucose transport and GLUT4 cell surface content, Wistar rats were subcutaneously injected with AICAR for 5 days in succession (1 mg/g body wt). Maximally insulin-stimulated (60 nmol/l) glucose uptake was markedly increased in epitrochlearis (EPI) muscle (average 63%, P < 0.001, n = 18-19) and in extensor digitorum longus muscle (average 26%, P < 0.001, n = 26-30). In contrast, administration of AICAR did not maximally influence insulin-stimulated glucose transport in soleus muscle. Studies of EPI muscle with the 4,4'-O-[2-[2-[2-[2-[2-[6-(biotinylamino)hexanoyl]amino]ethoxy]ethoxy] ethoxy]-4-(1-azi-2,2,2,-trifluoroethyl)benzoyl]amino-1,3-propanediyl]bis-D-mannose photolabeling technique showed a concomitant increase (average 68%, P < 0.02) in cell surface GLUT4 content after insulin exposure in AICAR-injected rats when compared with controls. In conclusion, 5 days of AICAR administration induces a pronounced fiber type-specific increase in insulin-stimulated glucose uptake and GLUT4 cell surface content in rat skeletal muscle with the greatest effect observed on white fast-twitch glycolytic muscles (EPI). These results are comparable with the eff...