Sucrose Non-fermenting AMPK-Related Kinase (SNARK) Regulates Exercise- and Ischemia-Stimulated Glucose Transport in the Heart

• Published in: Journal of cellular biochemistry Vol. 120; no. 1; pp. 685 - 696
• Main Authors: Sun, Xiang-lan, Lessard, Sarah J., An, Ding, Koh, Ho-Jin, Esumi, Hiroyasu, Hirshman, Michael F., Goodyear, Laurie J.
• Format: Journal Article
• Language: English
• Published: 07.09.2018
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.27425

The signaling mechanisms mediating myocardial glucose transport are not fully understood. Sucrose non-fermenting 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 SNARK and to knockdown endogenous SNARK. Overexpression of wild type 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 wild type littermates performed treadmill exercise. Exercise-stimulated glucose transport was decreased by ~50% in hearts from SNARK+/− mice. In summary, exercise and ischemia increase SNARK Thr 208 phosphorylation in the heart and SNARK regulates exercise- and ischemia-stimulated glucose transport. SNARK is a novel mediator of insulin-independent glucose transport in the heart.