Chronic treatment with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside increases insulin-stimulated glucose uptake and GLUT4 translocation in rat skeletal muscles in a fiber type-specific manner

Recent studies have demonstrated that chronic administration of AICAR (5-am inoimidazole-4-carboxamide-1-beta -D-ribofuranoside), an activator of the A MP-activated protein kinase, increases hexokinase activity and the contents of total GLUT4 and glycogen in rat skeletal muscles. To explore whether AI CAR also affects insulin-stimulated glucose transport and GLUT4 cell surfac e content. Wistar rats were subcutaneously injected with AICAR for 5 days i n succession (1 mg/g body wt). Maximally insulin-stimulated (60 nmol/l) glu cose 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 m aximally influence insulin-stimulated glucose transport in soleus muscle. S tudies of EPI muscle with the 4,4'-O-[2-[2-[2-[2[2-[6-(biotinylamino)hexano yl]amino] ethoxy]ethoxy] ethoxyl-4-(1-azi-2,2,2,-trifluoroethyl)benzoyl]ami no-1,3-propanediyl]bis-D-mannose photolabeling technique showed a concomita nt increase (average 68%, P < 0.02) in cell surface GLUT4 content after ins ulin exposure in AICAR-injected rats when compared with controls. In conclu sion, 5 days of AICAR administration induces a pronounced fiber type-specif ic increase in insulin-stimulated glucose uptake and GLUT4 cell surface con tent in rat skeletal muscle with the greatest effect observed on white fast -twitch glycolytic muscles (EPI). These results are comparable with the eff ects of chronic exercise training, and it brings the AMP-activated protein kinase into focus as a new interesting target for future pharmacological in tervention in insulin-resistant conditions.