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(Circulation Research. 2001;88:552.)
© 2001 American Heart Association, Inc.

Editorial

Roads to Survival

Insulin-Like Growth Factor-1 Signaling Pathways in Cardiac Muscle

Ping H. Wang

From the Departments of Medicine and Biological Chemistry, Division of Endocrinology, Diabetes, and Metabolism, University of California, Irvine, Calif.

Correspondence to Ping H. Wang, MD, Med Sci I, Room C240, University of California, Irvine, CA 92697. E-mail phwang@uci.edu

Key Words: insulin-like growth factor-1 • phosphoinositol-3'-kinase • Akt • apoptosis • heart

	Introduction

 
Insulin-like growth factor-1 (IGF-1) plays a role in the regulation of myocardial structure and function. IGF-1 is capable of improving cardiac muscle survival, growth, calcium signaling, and differentiation.¹ Among various actions of IGF-1 on heart, the ability of IGF-1 to counteract apoptosis of cardiomyocytes has drawn significant attention in recent years. IGF-1 suppresses myocardial apoptosis and improves myocardial function in various models of experimental cardiomyopathy.^{2 3 4 5} Compared with other growth factors, the survival effect of IGF-1 on myocardium is rather unique.

	More Than Just Phosphoinositol-3'-Kinase and Akt

 
Using an ex vivo model of perfused heart isolated from IGF-1 overexpressing transgenic mice, the study by Yamashita et al⁶ in this issue of Circulation Research demonstrated that disrupting the activation of Akt abolished the antiapoptotic effects of autocrine/paracrine IGF-1 during ischemia/reperfusion injury. Activation of p38 mitogen-activated protein (MAP) kinase has been previously implicated in myocardial injury during ischemia/reperfusion. These investigators confirmed previous studies that blocking p38 MAP kinase reduced myocardial apoptosis in wild-type heart. However, in this study, inhibiting p38 MAP kinase activation was accompanied by significant suppression of Akt activation during ischemia/reperfusion and increased apoptosis in the IGF-1 transgenic heart. The authors concluded that, on inhibiting p38 MAP kinase activation, the reduction of Akt activation in the transgenic myocardium disrupted the spatial balance between p38 MAP kinase and Akt activation and thus triggered more apoptosis during ischemia/reperfusion. In this study, inhibition of p38 MAP kinase was achieved with chemical inhibitor SB203580. One may argue that chemical inhibitors are not impeccably specific; thus the attenuation of Akt activation by . . . [Full Text of this Article]

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