Exercise increases human skeletal muscle insulin sensitivity via coordinated increases in microvascular perfusion and molecular signaling

Kim Anker Sjøberg, Christian Frøsig, Rasmus Kjøbsted, Lykke Sylow, Maximilian Kleinert, Andrew C Betik, Christopher S Shaw, Bente Kiens, Jørgen Wojtaszewski, Stephen Rattigan, Erik A. Richter, Glenn K McConell

Research output: Contribution to journalJournal articleResearchpeer-review

126 Citations (Scopus)

Abstract

Insulin resistance is a major health risk and although exercise clearly improves skeletal muscle insulin sensitivity, the mechanisms are unclear. Here we show that initiation of a euglycemic hyperinsulinemic clamp four hours after single-legged exercise in humans increased microvascular perfusion (determined by contrast enhanced ultrasound) by 65% in the exercised leg and 25% in the rested leg (p<0.05) and leg glucose uptake increased 50% more (p<0.05) in the exercised leg than the rested leg. Importantly, infusion of the nitric oxide synthase inhibitor L-NMMA into both femoral arteries reversed the insulin stimulated increase in microvascular perfusion in both legs and abrogated the greater glucose uptake in the exercised compared with the rested leg. Skeletal muscle phosphorylation of TBC1D4 Ser(318) and Ser(704) and glycogen synthase activity were greater in the exercised leg before insulin and increased similarly in both legs during the clamp and L-NMMA had no effect on these insulin-stimulated signaling pathways. Therefore, acute exercise increases insulin sensitivity of muscle by a coordinated increase in insulin-stimulated microvascular perfusion and molecular signaling at the level of TBC1D4 and glycogen synthase in muscle. This secures improved glucose delivery on the one hand and increased ability to take up and dispose of the delivered glucose on the other hand.

Original languageEnglish
JournalDiabetes
Volume66
Issue number6
Pages (from-to)1501-1510
Number of pages10
ISSN0012-1797
DOIs
Publication statusPublished - 2017

Keywords

  • Journal Article

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