Contraction-stimulated glucose transport in muscle is controlled by AMPK and mechanical stress but not sarcoplasmatic reticulum Ca(2+) release

Thomas E Jensen; Lykke Sylow; Adam J Rose; Agnete B Madsen; Yeliz Angin; Stine J Maarbjerg; Erik A Richter

doi:10.1016/j.molmet.2014.07.005

Contraction-stimulated glucose transport in muscle is controlled by AMPK and mechanical stress but not sarcoplasmatic reticulum Ca(2+) release

Mol Metab. 2014 Jul 28;3(7):742-53. doi: 10.1016/j.molmet.2014.07.005. eCollection 2014 Oct.

Authors

Thomas E Jensen¹, Lykke Sylow¹, Adam J Rose¹, Agnete B Madsen¹, Yeliz Angin¹, Stine J Maarbjerg¹, Erik A Richter¹

Affiliation

¹ Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, 2100 Copenhagen, Denmark.

Abstract

Understanding how muscle contraction orchestrates insulin-independent muscle glucose transport may enable development of hyperglycemia-treating drugs. The prevailing concept implicates Ca(2+) as a key feed forward regulator of glucose transport with secondary fine-tuning by metabolic feedback signals through proteins such as AMPK. Here, we demonstrate in incubated mouse muscle that Ca(2+) release is neither sufficient nor strictly necessary to increase glucose transport. Rather, the glucose transport response is associated with metabolic feedback signals through AMPK, and mechanical stress-activated signals. Furthermore, artificial stimulation of AMPK combined with passive stretch of muscle is additive and sufficient to elicit the full contraction glucose transport response. These results suggest that ATP-turnover and mechanical stress feedback are sufficient to fully increase glucose transport during muscle contraction, and call for a major reconsideration of the established Ca(2+) centric paradigm.

Keywords: AMPK; Ca2+; Exercise; Skeletal muscle; Stretch.