Chronic activation of 5′-AMP-activated protein kinase increases GLUT-4, hexokinase, and glycogen in muscle
Tóm tắt
This study was designed to determine whether chronic chemical activation of AMP-activated protein kinase (AMPK) would increase glucose transporter GLUT-4 and hexokinase in muscles similarly to periodic elevation of AMPK that accompanies endurance exercise training. The adenosine analog, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), has previously been shown to be taken up by cells and phosphorylated to form a compound (5-aminoimidazole-4-carboxamide ribonucleotide) that mimics the effect of AMP on AMPK. A single injection of AICAR resulted in a marked increase in AMPK in epitrochlearis and gastrocnemius/plantaris muscles 60 min later. When rats were injected with AICAR (1 mg/g body wt) for 5 days in succession and were killed 1 day after the last injection, GLUT-4 was increased by 100% in epitrochlearis muscle and by 60% in gastrocnemius muscle in response to AICAR. Hexokinase was also increased ∼2.5-fold in the gastrocnemius/plantaris. Gastrocnemius glycogen content was twofold higher in AICAR-treated rats than in controls. Chronic chemical activation of AMPK, therefore, results in increases in GLUT-4 protein, hexokinase activity, and glycogen, similarly to those induced by endurance training.
Từ khóa
Tài liệu tham khảo
Bergeron R., 1999, Am. J. Physiol., 276, E938
Etgen G. J., 1997, Am. J. Physiol., 272, E864
Hassid W. Z., 1957, Methods Enzymol., 3, 35
Hayashi T., 1998, Diabetes, 47, 1369
Hayashi T., 1997, Am. J. Physiol., 273, E1039
Merrill G. F., 1997, Am. J. Physiol., 273, E1107
Ruderman N. B., 1999, Am. J. Physiol., 276, E1
Vincent M. F., 1991, Adv. Exp. Med. Biol., 309, 1991
Winder W. W., 1996, Am. J. Physiol., 270, E299
Winder W. W., 1999, Am. J. Physiol., 277, E1