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

Abstract

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 Thr208 , a site critical for SNARK activity. Mice were treated with exercise, ischemia, submaximal insulin, or maximal insulin. Treadmill exercise slightly, but significantly increased SNARK Thr208 phosphorylation. Ischemia also increased SNARK Thr208 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 ~50% in hearts from SNARK+/- mice. In summary, exercise and ischemia increase SNARK Thr208 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.

• Authors: Xiang-Lan Sun, Sarah J Lessard, Ding An, Ho-Jin Koh, Hiroyasu Esumi, Michael F Hirshman, Laurie J Goodyear
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 120 Issue 1 Pg. 685-696 (01 2019) ISSN: 1097-4644 [Electronic] United States
• PMID: 30256437 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• Insulin
• Protein Serine-Threonine Kinases
• SNARK protein, mouse
• Glucose

Topics

• Animals
• Biological Transport
• Cell Line, Tumor
• Coronary Vessels (metabolism)
• Gene Knockdown Techniques
• Glucose (metabolism)
• Insulin (pharmacology)
• Ischemia (metabolism)
• Male
• Mice
• Mice, Inbred ICR
• Mice, Knockout
• Myocardium (metabolism)
• Myocytes, Cardiac (metabolism)
• Phosphorylation
• Physical Conditioning, Animal
• Protein Serine-Threonine Kinases (genetics)
• Signal Transduction (drug effects)