Chronic activation of 5′-AMP-activated protein kinase increases GLUT-4, hexokinase, and glycogen in muscle

Journal of Applied Physiology - Tập 87 Số 5 - Trang 1990-1995 - 1999
Burton Holmes1, E. J. Kurth-Kraczek1, W. W. Winder1
1Department of Zoology, Brigham Young University, Provo, Utah, 84602

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

10.2337/diab.43.7.862

Etgen G. J., 1997, Am. J. Physiol., 272, E864

10.1006/bbrc.1997.7587

10.2337/diab.41.4.465

10.1172/JCI1557

10.1146/annurev.med.49.1.235

10.1152/jappl.1995.79.5.1562

10.1007/BF00400207

10.1146/annurev.biochem.67.1.821

Hassid W. Z., 1957, Methods Enzymol., 3, 35

Hayashi T., 1998, Diabetes, 47, 1369

Hayashi T., 1997, Am. J. Physiol., 273, E1039

Holloszy J. O., 1996, Rev. Physiol. Biochem. Pharmacol., 128, 99, 10.1007/3-540-61343-9_8

10.1152/jappl.1998.84.3.798

10.1152/jappl.1998.85.1.133

10.2165/00007256-199724050-00004

10.1172/JCI118724

10.2337/diabetes.48.5.1192

10.1006/bbrc.1998.9940

10.2337/diabetes.48.8.1667

McGarry J. D., 1978, J. Biol. Chem., 253, 8291, 10.1016/S0021-9258(17)34394-6

Merrill G. F., 1997, Am. J. Physiol., 273, E1107

10.1152/ajpcell.1993.265.6.C1597

10.2337/diab.39.7.865

Ren J. M., 1994, J. Biol. Chem., 269, 14396, 10.1016/S0021-9258(17)36636-X

Ruderman N. B., 1999, Am. J. Physiol., 276, E1

10.1006/bbrc.1997.7516

Uyeda K., 1965, J. Biol. Chem., 240, 4682, 10.1016/S0021-9258(18)97009-2

10.1007/BF02658500

Vincent M. F., 1991, Adv. Exp. Med. Biol., 309, 1991

10.2165/00007256-199825010-00003

Winder W. W., 1996, Am. J. Physiol., 270, E299

Winder W. W., 1999, Am. J. Physiol., 277, E1