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

TY - JOUR

T1 - Contraction-stimulated glucose transport in muscle is controlled by AMPK and mechanical stress but not sarcoplasmatic reticulum Ca2+ release

AU - Jensen, Thomas Elbenhardt

AU - Sylow, Lykke

AU - Rose, Adam John

AU - Madsen, Agnete Louise Bjerregaard

AU - Angin, Yeliz

AU - Maarbjerg, Stine J

AU - Richter, Erik

N1 - CURIS 2014 NEXS 324

PY - 2014/10/1

Y1 - 2014/10/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.molmet.2014.07.005

DO - 10.1016/j.molmet.2014.07.005

M3 - Journal article

C2 - 25353002

SN - 2212-8778

VL - 3

SP - 742

EP - 753

JO - Molecular Metabolism

JF - Molecular Metabolism

IS - 7

ER -