Jensen, Thomas Elbenhardt4; Sylow, Lykke4; Rose, Adam John2; Madsen, Agnete Louise Bjerregaard4; Angin, Yeliz4; Maarbjerg, Stine J3; Richter, Erik4
1 Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet2 Joint Division Molecular Metabolic Control, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ) Heidelberg3 Diabetes Research Unit, Novo Nordisk A/S4 Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet
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.
Molecular Metabolism, 2014, Vol 3, Issue 7, p. 742-753