AMPK, insulin resistance, and the metabolic syndrome

被引:684
作者
Ruderman, Neil B. [1 ,2 ,3 ]
Carling, David [4 ]
Prentki, Marc [5 ,6 ,7 ,8 ]
Cacicedo, Jose M. [1 ,2 ,3 ]
机构
[1] Boston Univ, Diabet & Metab Res Unit, Sch Med, Boston, MA 02118 USA
[2] Boston Univ, Dept Med, Sch Med, Boston, MA 02118 USA
[3] Boston Univ, Endocrinol Sect, Sch Med, Boston, MA 02118 USA
[4] Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Hammersmith Hosp, Cellular Stress Grp, London, England
[5] Univ Montreal, Montreal Diabet Res Ctr, Montreal, PQ, Canada
[6] Univ Montreal, CRCHUM, Montreal, PQ, Canada
[7] Univ Montreal, Dept Nutr, Montreal, PQ H3C 3J7, Canada
[8] Univ Montreal, Dept Biochem, Montreal, PQ H3C 3J7, Canada
基金
英国医学研究理事会;
关键词
ACTIVATED PROTEIN-KINASE; ACETYL-COA CARBOXYLASE; MUSCLE GLUCOSE-METABOLISM; NITRIC-OXIDE SYNTHASE; FATTY-ACID OXIDATION; ADIPOSE-TISSUE; MALONYL-COA; SKELETAL-MUSCLE; ENDOTHELIAL-CELLS; BARIATRIC SURGERY;
D O I
10.1172/JCI67227
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Insulin resistance (IR) and hyperinsulinemia are hallmarks of the metabolic syndrome, as are central adiposity, d.yslipidemia, and a predisposition to type 2 diabetes, atherosclerotic cardiovascular disease, hypertension, and certain cancers. Regular exercise and calorie restriction have long been known to increase insulin sensitivity and decrease the prevalence of these disorders. The subsequent identification of AMP-activated protein kinase (AMPK) and its activation by exercise and fuel deprivation have led to studies of the effects of AMPK on both IR and metabolic syndrome-related diseases. In this review, we evaluate this body of literature, with special emphasis on the hypothesis that dysregulation of AMPK is both a pathogenic factor for these disorders in humans and a target for their prevention and therapy.
引用
收藏
页码:2764 / 2772
页数:9
相关论文
共 151 条
[51]   AMP-activated protein kinase-an energy sensor that regulates all aspects of cell function [J].
Hardie, D. Grahame .
GENES & DEVELOPMENT, 2011, 25 (18) :1895-1908
[52]   AMP-activated protein kinase: also regulated by ADP? [J].
Hardie, D. Grahame ;
Carling, David ;
Gamblin, Steven J. .
TRENDS IN BIOCHEMICAL SCIENCES, 2011, 36 (09) :470-477
[53]   Body mass index-independent inflammation in omental adipose tissue associated with insulin resistance in morbid obesity [J].
Hardy, Olga T. ;
Perugini, Richard A. ;
Nicoloro, Sarah M. ;
Gallagher-Dorval, Karen ;
Puri, Vishwajeet ;
Straubhaar, Juerg ;
Czech, Michael P. .
SURGERY FOR OBESITY AND RELATED DISEASES, 2011, 7 (01) :60-67
[54]   Metformin inhibits cytokine-induced nuclear factor κB activation via AMP-activated protein kinase activation in vascular endothelial cells [J].
Hattori, Yoshiyuki ;
Suzuki, Kunihiro ;
Hattori, Sachiko ;
Kasai, Kikuo .
HYPERTENSION, 2006, 47 (06) :1183-1188
[55]   The Ancient Drug Salicylate Directly Activates AMP-Activated Protein Kinase [J].
Hawley, Simon A. ;
Fullerton, Morgan D. ;
Ross, Fiona A. ;
Schertzer, Jonathan D. ;
Chevtzoff, Cyrille ;
Walker, Katherine J. ;
Peggie, Mark W. ;
Zibrova, Darya ;
Green, Kevin A. ;
Mustard, Kirsty J. ;
Kemp, Bruce E. ;
Sakamoto, Kei ;
Steinberg, Gregory R. ;
Hardie, D. Grahame .
SCIENCE, 2012, 336 (6083) :918-922
[56]   AMPK activity and isoform protein expression are similar in muscle of obese subjects with and without type 2 diabetes [J].
Hojlund, K ;
Mustard, KJ ;
Stæhr, P ;
Hardie, DG ;
Beck-Nielsen, H ;
Richter, EA ;
Wojtaszewski, JFP .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2004, 286 (02) :E239-E244
[57]   SIRT1 regulates hepatocyte lipid metabolism through activating AMP-activated protein kinase [J].
Hou, Xiuyun ;
Xu, Shanqin ;
Maitland-Toolan, Karlene A. ;
Sato, Kaori ;
Jiang, Bingbing ;
Ido, Yasuo ;
Lan, Fan ;
Walsh, Kenneth ;
Wierzbicki, Michel ;
Verbeuren, Tony J. ;
Cohen, Richard A. ;
Zang, Mengwei .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (29) :20015-20026
[58]   Reactive oxygen species have a causal role in multiple forms of insulin resistance [J].
Houstis, N ;
Rosen, ED ;
Lander, ES .
NATURE, 2006, 440 (7086) :944-948
[59]   Hyperglycemia-induced apoptosis in human umbilical vein endothelial cells - Inhibition by the AMP-activated protein kinase activation [J].
Ido, Y ;
Carling, D ;
Ruderman, N .
DIABETES, 2002, 51 (01) :159-167
[60]   Adiponectin and AdipoR1 regulate PGC-1α and mitochondria by Ca2+ and AMPK/SIRT1 [J].
Iwabu, Masato ;
Yamauchi, Toshimasa ;
Okada-Iwabu, Miki ;
Sato, Koji ;
Nakagawa, Tatsuro ;
Funata, Masaaki ;
Yamaguchi, Mamiko ;
Namiki, Shigeyuki ;
Nakayama, Ryo ;
Tabata, Mitsuhisa ;
Ogata, Hitomi ;
Kubota, Naoto ;
Takamoto, Iseki ;
Hayashi, Yukiko K. ;
Yamauchi, Naoko ;
Waki, Hironori ;
Fukayama, Masashi ;
Nishino, Ichizo ;
Tokuyama, Kumpei ;
Ueki, Kohjiro ;
Oike, Yuichi ;
Ishii, Satoshi ;
Hirose, Kenzo ;
Shimizu, Takao ;
Touhara, Kazushige ;
Kadowaki, Takashi .
NATURE, 2010, 464 (7293) :1313-1319