This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tian, R. Articles by Balschi, J. A. Search for Related Content PubMed PubMed Citation Articles by Tian, R. Articles by Balschi, J. A. Related Collections Related Article

(Circulation Research. 2006;99:3.)
© 2006 American Heart Association, Inc.

Editorials

Interaction of Insulin and AMPK in the Ischemic Heart

Another Chapter in the Book of Metabolic Therapy?

Rong Tian, James A. Balschi

From the NMR Laboratory for Physiological Chemistry, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Rong Tian, MD, PhD, 221 Longwood Avenue, Room 252, Boston, MA 02115. E-mail rtian@rics.bwh.harvard.edu

See related article, pages 61–68

Key Words: insulin • AMPK • glucose • myocardial ischemia • metabolic modulation

An extract of the first 250 words of the full text is provided, because this article has no abstract.

There has been a longstanding interest in the development of metabolic modulations to improve the outcome of myocardial ischemia. The glucose-insulin-potassium (GIK) regimen presents the classic example of such a quest. For more than four decades since GIK was first described, substantial evidence from animal research and small size clinical studies has supported the efficacy of GIK treatment for acute myocardial ischemia.^1–3 However, a recent large clinical trial, CREATE-ECLA, showed no effect of GIK in patients with acute ST-segment elevation myocardial infarction.^1,4 Although this is extremely disappointing for supporters of metabolic treatment, careful evaluations of why GIK got lost in translation will benefit future development of therapeutic strategies based on metabolic principles. The study by Folmes et al published in this issue of Circulation Research sheds some light on this matter.⁵

Decreased perfusion during myocardial ischemia limits the delivery of oxygen and nutrients and decreases oxidative metabolism. Under these conditions, increased glycolytic ATP production becomes a critical energy source (Figure). Several mechanisms have been proposed to account for the increases in glucose uptake and glycolysis during myocardial ischemia. These include: -adrenergic mechanisms, p38 activation, and, more recently, stimulation of AMPK-activated protein kinase (AMPK).^6–9 AMPK acts as an intracellular energy sensor. Its activity is highly sensitive to the cellular AMP to ATP ratio. AMPK activity markedly increases in response to energy depletion (increased AMP/ATP) during myocardial ischemia.^8,10 Previous studies suggested that the increased AMPK activity promoted glycolytic ATP production and, thereby, protected against ischemic injury.^8,11 It was also suggested, . . . [Full Text of this Article]

Related Article:

Fatty Acids Attenuate Insulin Regulation of 5'-AMP–Activated Protein Kinase and Insulin Cardioprotection After Ischemia

Clifford D.L. Folmes, Alexander S. Clanachan, and Gary D. Lopaschuk
Circ. Res. 2006 99: 61-68. [Abstract] [Full Text] [PDF]

This article has been cited by other articles:

				Y. Wang, L. Tao, Y. Yuan, W. B. Lau, R. Li, B. L. Lopez, T. A. Christopher, R. Tian, and X.-L. Ma Cardioprotective effect of adiponectin is partially mediated by its AMPK-independent antinitrative action Am J Physiol Endocrinol Metab, August 1, 2009; 297(2): E384 - E391. [Abstract] [Full Text] [PDF]

				Y. Wang, E. Gao, L. Tao, W. B. Lau, Y. Yuan, B. J. Goldstein, B. L. Lopez, T. A. Christopher, R. Tian, W. Koch, et al. AMP-Activated Protein Kinase Deficiency Enhances Myocardial Ischemia/Reperfusion Injury but Has Minimal Effect on the Antioxidant/Antinitrative Protection of Adiponectin Circulation, February 17, 2009; 119(6): 835 - 844. [Abstract] [Full Text] [PDF]

				L. Bertrand, S. Horman, C. Beauloye, and J.-L. Vanoverschelde Insulin signalling in the heart Cardiovasc Res, July 15, 2008; 79(2): 238 - 248. [Abstract] [Full Text] [PDF]

				T. Doenst, H. Bugger, M. Schwarzer, G. Faerber, M. A. Borger, and F. W. Mohr Three good reasons for heart surgeons to understand cardiac metabolism Eur. J. Cardiothorac. Surg., May 1, 2008; 33(5): 862 - 871. [Abstract] [Full Text] [PDF]

				C. J. Zuurbier, F. J. Hoek, J. van Dijk, N. G. Abeling, J. C. M. Meijers, J. H. M. Levels, E. de Jonge, B. A. de Mol, and H. B. Van Wezel Perioperative hyperinsulinaemic normoglycaemic clamp causes hypolipidaemia after coronary artery surgery Br. J. Anaesth., April 1, 2008; 100(4): 442 - 450. [Abstract] [Full Text] [PDF]

				V. W. Dolinsky and J. R. B. Dyck Role of AMP-activated protein kinase in healthy and diseased hearts Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2557 - H2569. [Abstract] [Full Text] [PDF]