Physiological role of AMP-activated protein kinase in the heart: graded activation during exercise

Author:

Coven David L.,Hu Xiaoyue,Cong Lin,Bergeron Raynald,Shulman Gerald I.,Hardie D. Grahame,Young Lawrence H.

Abstract

AMP-activated protein kinase (AMPK) is emerging as a key signaling pathway that modulates cellular metabolic processes. In skeletal muscle, AMPK is activated during exercise. Increased myocardial substrate metabolism during exercise could be explained by AMPK activation. Although AMPK is known to be activated during myocardial ischemia, it remains uncertain whether AMPK is activated in response to the physiological increases in cardiac work associated with exercise. Therefore, we evaluated cardiac AMPK activity in rats at rest and after 10 min of treadmill running at moderate (15% grade, 16 m/min) or high (15% grade, 32 m/min) intensity. Total AMPK activity in the heart increased in proportion to exercise intensity ( P < 0.05). AMPK activity associated with the α2-catalytic subunit increased 2.8 ± 0.4-fold ( P < 0.02 vs. rest) and 4.5 ± 0.6-fold ( P < 0.001 vs. rest) with moderate- and high-intensity exercise, respectively. AMPK activity associated with the α1-subunit increased to a lesser extent. Phosphorylation of the Thr172-regulatory site on AMPK α-catalytic subunits increased during exercise ( P < 0.001). There was no increase in Akt phosphorylation during exercise. The changes in AMPK activity during exercise were associated with physiological AMPK effects (GLUT4 translocation to the sarcolemma and ACC phosphorylation). Thus cardiac AMPK activity increases progressively with exercise intensity, supporting the hypothesis that AMPK has a physiological role in the heart.

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology,Endocrinology, Diabetes and Metabolism

Reference61 articles.

1. The subcellular localization of acetyl-CoA carboxylase 2

2. Human acetyl-CoA carboxylase: characterization, molecular cloning, and evidence for two isoforms.

3. Continuous Fatty Acid Oxidation and Reduced Fat Storage in Mice Lacking Acetyl-CoA Carboxylase 2

4. Asefaw S, Russell RR, Bergeron R, Hu J, Dione D, Sinusas AJ, and Young LH. Stimulation of AMP-activated protein kinase by AICAR increases heart glucose uptake and GLUT4 and GLUT1 translocation to the sarcolemma in vivo (Abstract). Diabetes 48, Suppl 1: A273, 1999.

5. The stimulation of heart glycolysis by increased workload does not require AMP-activated protein kinase but a wortmannin-sensitive mechanism

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3