Contraction-stimulated glucose transport in muscle is controlled by AMPK and mechanical stress but not sarcoplasmatic reticulum Ca2+ release

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

Research output: Contribution to journalArticleResearchpeer-review

60 Citations (Scopus)

Abstract

Understanding how muscle contraction orchestrates insulin-independent muscle glucose transport may enable development of hyperglycemia-treating drugs. The prevailing concept implicates Ca2+ 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 Ca2+ 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 Ca2+ centric paradigm.

Original languageEnglish
Pages (from-to)742-753
Number of pages12
JournalMolecular Metabolism
Volume3
Issue number7
DOIs
Publication statusPublished - 1 Oct 2014
Externally publishedYes

Keywords

  • AMPK
  • Ca
  • Exercise
  • Skeletal muscle
  • Stretch

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