AMP-activated protein kinase activity and glucose uptake in rat skeletal muscle

被引:186
作者
Musi, N
Hayashi, T
Fujii, N
Hirshman, MF
Witters, LA
Goodyear, LJ
机构
[1] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA
[2] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA
[3] Harvard Univ, Sch Med, Boston, MA 02215 USA
[4] Dartmouth Med Sch, Dept Med & Biochem, Endocrine Metab Div, Hanover, NH USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2001年 / 280卷 / 05期
关键词
adenosine 5 '-monophosphate-activated protein kinase; contraction;
D O I
10.1152/ajpendo.2001.280.5.E677
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The AMP-activated protein kinase (AMPK) has been hypothesized to mediate contraction and 5-aminoimidazole-4-carboxamide 1-beta -D-ribonucleoside (AICAR)-induced increases in glucose uptake in skeletal muscle. The purpose of the current study was to determine whether treadmill exercise and isolated muscle contractions in rat skeletal muscle increase the activity of the AMPK alpha1 and AMPK alpha2 catalytic subunits in a dose-dependent manner and to evaluate the effects of the putative AMPK inhibitors adenine 9-beta -D-arabinofuranoside (ara-A), 8-bromo-AMP, and iodotubercidin on AMPK activity and 3-O-methyl-D-glucose (3-MG) uptake. There were dose-dependent increases in AMPK alpha2 activity and 3-MG uptake in rat epitrochlearis muscles with treadmill running exercise but no effect of exercise on AMPK alpha1 activity. Tetanic contractions of isolated epitrochlearis muscles in vitro significantly increased the activity of both AMPK isoforms in a dose-dependent manner and at a similar rate compared with increases in 3-MG uptake. In isolated muscles, the putative AMPK inhibitors ara-A, 8-bromo-AMP, and iodotubercidin fully inhibited AICAR-stimulated AMPK alpha2 activity and 3-MG uptake but had little effect on AMPK alpha1 activity, in contrast, these compounds had absent or minimal effects on contraction-stimulated AMPK alpha1 and -alpha2 activity and 3-MG uptake. Although the AMPK alpha1 and -alpha2 isoforms are activated during tetanic muscle contractions in vitro, in fast-glycolytic fibers, the activation of AMPK alpha2-containing complexes may be more important in regulating exercise-mediated skeletal muscle metabolism in vivo. Development of new compounds will be required to study contraction regulation of AMPK by pharmacological inhibition.
引用
收藏
页码:E677 / E684
页数:8
相关论文
共 44 条
[1]   Stimulation of AMP-activated protein kinase (AMPK) is associated with enhancement of Glut1-mediated glucose transport [J].
Abbud, W ;
Habinowski, S ;
Zhang, JZ ;
Kendrew, J ;
Elkairi, FS ;
Kemp, BE ;
Witters, LA ;
Ismail-Beigi, F .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2000, 380 (02) :347-352
[2]   GLYCOGEN, LACTATE, AND ALANINE CHANGES IN MUSCLE-FIBER TYPES DURING GRADED EXERCISE [J].
BALDWIN, KM ;
CAMPBELL, PJ ;
COOKE, DA .
JOURNAL OF APPLIED PHYSIOLOGY, 1977, 43 (02) :288-291
[3]   Effect of AMPK activation on muscle glucose metabolism in conscious rats [J].
Bergeron, R ;
Russell, RR ;
Young, LH ;
Ren, JM ;
Marcucci, M ;
Lee, A ;
Shulman, GI .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 1999, 276 (05) :E938-E944
[4]   EFFECTS OF PHYSICAL-TRAINING AND DIET THERAPY ON CARBOHYDRATE-METABOLISM IN PATIENTS WITH GLUCOSE-INTOLERANCE AND NON-INSULIN-DEPENDENT DIABETES-MELLITUS [J].
BOGARDUS, C ;
RAVUSSIN, E ;
ROBBINS, DC ;
WOLFE, RR ;
HORTON, ES ;
SIMS, EAH .
DIABETES, 1984, 33 (04) :311-318
[5]   AMPK signaling in contracting human skeletal muscle: acetyl-CoA carboxylase and NO synthase phosphorylation [J].
Chen, ZP ;
McConell, GK ;
Michell, BJ ;
Snow, RJ ;
Canny, BJ ;
Kemp, BE .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2000, 279 (05) :E1202-E1206
[6]   TISSUE DISTRIBUTION OF THE AMP-ACTIVATED PROTEIN-KINASE, AND LACK OF ACTIVATION BY CYCLIC-AMP-DEPENDENT PROTEIN-KINASE, STUDIED USING A SPECIFIC AND SENSITIVE PEPTIDE ASSAY [J].
DAVIES, SP ;
CARLING, D ;
HARDIE, DG .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1989, 186 (1-2) :123-128
[7]  
Dean DJ, 2000, DIABETES, V49, pA193
[8]   Dissociation of AMP-activated protein kinase activation and glucose transport in contracting slow-twitch muscle [J].
Derave, W ;
Ai, H ;
Ihlemann, J ;
Witters, LA ;
Kristiansen, S ;
Richter, EA ;
Ploug, T .
DIABETES, 2000, 49 (08) :1281-1287
[9]   Exercise induces isoform-specific increase in 5′AMP-activated protein kinase activity in human skeletal muscle [J].
Fujii, N ;
Hayashi, T ;
Hirshman, MF ;
Smith, JT ;
Habinowski, SA ;
Kaijser, L ;
Mu, J ;
Ljungqvist, O ;
Birnbaum, MJ ;
Witters, LA ;
Thorell, A ;
Goodyear, LJ .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 273 (03) :1150-1155
[10]   Exercise, glucose transport, and insulin sensitivity [J].
Goodyear, LJ ;
Kahn, BB .
ANNUAL REVIEW OF MEDICINE, 1998, 49 :235-261