Sucrose nonfermenting AMPK-related kinase (SNARK) regulates exercise-stimulated and ischemia-stimulated glucose transport in the heart

被引：5
|
作者：
Sun, Xiang-Lan [1 ,2 ,3 ]
Lessard, Sarah J. [2 ,3 ]
An, Ding [2 ,3 ]
Koh, Ho-Jin [2 ,3 ]
Esumi, Hiroyasu [4 ]
Hirshman, Michael F. [2 ,3 ]
Goodyear, Laurie J. [2 ,3 ]
机构：
[1] Shandong Univ, Dept Endocrinol, Shandong Prov Hosp, Jinan, Shandong, Peoples R China
[2] Harvard Med Sch, Integrat Physiol & Metab Sect, Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA
[3] Harvard Med Sch, Dept Med, One Joslin Pl, Boston, MA 02215 USA
[4] Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Canc Physiol Project, Kashiwa, Chiba, Japan
来源：
JOURNAL OF CELLULAR BIOCHEMISTRY | 2019年 / 120卷 / 01期
基金：
美国国家卫生研究院;
关键词：
Akt substrate of 160 kDa; glycogen; HL1; cardiomyocytes; insulin; ACTIVATED PROTEIN-KINASE; SKELETAL-MUSCLE; INSULIN RESPONSIVENESS; CELL-LINE; IDENTIFICATION; LKB1; PHOSPHORYLATION; INHIBITION; WORTMANNIN; DISEASE;
D O I：
10.1002/jcb.27425
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The signaling mechanisms mediating myocardial glucose transport are not fully understood. Sucrose nonfermenting AMP-activated protein kinase (AMPK)-related kinase (SNARK) is an AMPK-related protein kinase that is expressed in the heart and has been implicated in contraction-stimulated glucose transport in mouse skeletal muscle. We first determined if SNARK is phosphorylated on Thr(208), a site critical for SNARK activity. Mice were treated with exercise, ischemia, submaximal insulin, or maximal insulin. Treadmill exercise slightly, but significantly increased SNARK Thr(208) phosphorylation. Ischemia also increased SNARK Thr(208) phosphorylation, but there was no effect of submaximal or maximal insulin. HL1 cardiomyocytes were used to overexpress wild-type (WT) SNARK and to knockdown endogenous SNARK. Overexpression of WT SNARK had no effect on ischemia-stimulated glucose transport; however, SNARK knockdown significantly decreased ischemia-stimulated glucose transport. SNARK overexpression or knockdown did not alter insulin-stimulated glucose transport or glycogen concentrations. To study SNARK function in vivo, SNARK heterozygous knockout mice (SNARK(+/-)) and WT littermates performed treadmill exercise. Exercise-stimulated glucose transport was decreased by similar to 50% in hearts from SNARK(+/-) mice. In summary, exercise and ischemia increase SNARK Thr(208) phosphorylation in the heart and SNARK regulates exercise-stimulated and ischemia-stimulated glucose transport. SNARK is a novel mediator of insulin-independent glucose transport in the heart.
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收藏
页码：685 / 696
页数：12
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