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 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:	Refereed Article
Research Division:	Biomedical and Clinical Sciences
Research Group:	Clinical sciences
Research Field:	Endocrinology
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Clinical health not elsewhere classified
UTAS Author:	Rattigan, S (Professor Stephen Rattigan)
ID Code:	117432
Year Published:	2017
Web of Science® Times Cited:	91
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2017-06-14
Last Modified:	2018-06-05
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