Increased expression of GLUT-4 and hexokinase in rat epitrochlearis muscles exposed to AICAR in vitro

Exercise acutely stimulates muscle glucose transport and also brings about an adaptive increase in the capacity of muscle for glucose uptake by induci ng increases in GLUT-4 and hexokinase.(1) Recent studies have provided evid ence that activation of AMP protein kinase (AMPK) is involved in the stimul ation of glucose transport by exercise. The purpose of this study was to de termine whether activation of AMPK is also involved in mediating the adapti ve increases in GLUT-4 and hexokinase. To this end, we examined the effect of incubating rat epitrochlearis muscles in culture medium for 18 h in the presence or absence of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR ), which enters cells and is converted to the AMP analog ZMP, thus activati ng AMPK. Exposure of muscles to 0.5 mM AICAR in vitro for 18 h resulted in an similar to 50% increase in GLUT-4 protein and an similar to 80% increase in hexokinase. This finding provides strong evidence in support of the hyp othesis that the activation of AMPK that occurs in muscle during exercise i s involved in mediating the adaptive increases in GLUT-4 and hexokinase.