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

Sjoberg, KA, Frosig, C, Kjobsted, R, Sylow, L, Kleinert, M, Betik, AC, Shaw, CS, Kiens, B, Wojtaszewski, JFP, Rattigan, S ORCID: 0000-0001-6172-3040, Richter, EA and McConell, GK 2017 , 'Exercise increases human skeletal muscle insulin sensitivity via coordinated increases in microvascular perfusion and molecular signaling' , Diabetes, vol. 66, no. 6 , pp. 1501-1510 , doi: 10.2337/db16-1327.

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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 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 P 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 Ser318 and Ser704 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.

Item Type: Article
Authors/Creators:Sjoberg, KA and Frosig, C and Kjobsted, R and Sylow, L and Kleinert, M and Betik, AC and Shaw, CS and Kiens, B and Wojtaszewski, JFP and Rattigan, S and Richter, EA and McConell, GK
Journal or Publication Title: Diabetes
Publisher: Amer Diabetes Assoc
ISSN: 0012-1797
DOI / ID Number: 10.2337/db16-1327
Copyright Information:

© 2017 by the American Diabetes Association.

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