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

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journal contribution
posted on 2017-06-01, 00:00 authored by K A Sjøberg, C Frøsig, R Kjøbsted, L Sylow, M Kleinert, Andrew BetikAndrew Betik, Chris ShawChris Shaw, B Kiens, J F P Wojtaszewski, S Rattigan, E A Richter, G K McConell
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 4 h after single-legged exercise in humans increased microvascular perfusion (determined by contrastenhanced ultrasound) by 65% in the exercised leg and 25% in the rested leg (P < 0.05) and that leg glucose uptake increased 50% more (P < 0.05) in the exercised leg than in the rested leg. Importantly, infusion of the nitric oxide synthase inhibitor L-N G -monomethyl- L-arginine acetate (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.

History

Journal

Diabetes

Volume

66

Issue

6

Pagination

1501 - 1510

Publisher

American Diabetes Association

Location

Arlington, Va.

ISSN

0012-1797

eISSN

1939-327X

Language

eng

Publication classification

C Journal article; C1 Refereed article in a scholarly journal

Copyright notice

2017, American Diabetes Association