J Clin Invest 116(7): 1776-1783

AMP-activated protein kinase signaling in metabolic regulation

Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

Address correspondence to: Juleen R. Zierath, Karolinska Institutet, Department of Molecular Medicine and Surgery, Section of Integrative Physiology, von Eulers väg 4, 4th floor, S-171 77 Stockholm, Sweden. Phone: 46-8-524-875-80; Fax: 46-8-33-54-36; E-mail: es.ik@htareiZ.neeluJ .

Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

Abstract

AMP-activated protein kinase (AMPK) is an energy sensor that regulates cellular metabolism. When activated by a deficit in nutrient status, AMPK stimulates glucose uptake and lipid oxidation to produce energy, while turning off energy-consuming processes including glucose and lipid production to restore energy balance. AMPK controls whole-body glucose homeostasis by regulating metabolism in multiple peripheral tissues, such as skeletal muscle, liver, adipose tissues, and pancreatic β cells — key tissues in the pathogenesis of type 2 diabetes. By responding to diverse hormonal signals including leptin and adiponectin, AMPK serves as an intertissue signal integrator among peripheral tissues, as well as the hypothalamus, in the control of whole-body energy balance.

Abstract

Acknowledgments

The authors are grateful to current and former members of the laboratory for helpful discussion. Support has been obtained from the Swedish Research Council, the Swedish Diabetes Association, the Foundation for Scientific Studies of Diabetology, the Strategic Research Foundation (INGVAR II), and the Commission of the European Communities (contract no. LSHM-CT-2004-005272 EXGENESIS and contract no. LSHM-CT-2004-512013 EUGENE2). Y.C. Long is supported by scholarship from the Karolinska Institutet.

Acknowledgments

Footnotes

Nonstandard abbreviations used: ACC, acetyl-CoA carboxylase; AICAR, 5-aminoimidazole-4-carboxamide riboside; AMPK, AMP-activated protein kinase; AS160, Akt substrate of 160 kDa; CaMKK, calmodulin-dependent protein kinase kinase; CREB, cAMP response element–binding protein; G6Pase, glucose-6-phosphatase; GLUT4, glucose transporter 4; PEPCK, phosphoenolpyruvate carboxykinase; PGC-1, PPARγ coactivator 1; T2D, type 2 diabetes; TORC2, transducer of regulated CREB activity 2.

Conflict of interest: The laboratory of J.R. Zierath receives research funding from Arexis AB, Sweden, which investigates pharmaceutical targeting of AMPK.

Citation for this article:J. Clin. Invest.116:1776–1783 (2006). doi:10.1172/JCI29044.

Footnotes

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