title: Contraction-stimulated glucose transport in muscle is controlled by AMPK and mechanical stress but not sarcoplasmatic reticulum Ca(2+) release.
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.
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Jensen
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Lykke
authors.initials: L
authors.lastname: Sylow
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Rose
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Agnete B
authors.initials: AB
authors.lastname: Madsen
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Yeliz
authors.initials: Y
authors.lastname: Angin
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Stine J
authors.initials: SJ
authors.lastname: Maarbjerg
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Richter
keywords: AMPK; Ca2+; Exercise; Skeletal muscle; Stretch