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Exercise Increases Human Skeletal Muscle Insulin Sensitivity via Coordinated Increases in Microvascular Perfusion and Molecular Signaling
- Source :
- Diabetes. 66:1501-1510
- Publication Year :
- 2017
- Publisher :
- American Diabetes Association, 2017.
-
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 contrast-enhanced 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-NG-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.
- Subjects :
- Male
0301 basic medicine
Endocrinology, Diabetes and Metabolism
Glucose uptake
medicine.medical_treatment
Contrast Media
0302 clinical medicine
Insulin
Enzyme Inhibitors
Phosphorylation
Ultrasonography
biology
GTPase-Activating Proteins
Glucose clamp technique
Healthy Volunteers
Femoral Artery
Glycogen Synthase
medicine.anatomical_structure
Signal Transduction
Adult
medicine.medical_specialty
030209 endocrinology & metabolism
Carbohydrate metabolism
Young Adult
03 medical and health sciences
Insulin resistance
Internal medicine
Internal Medicine
medicine
Humans
Hypoglycemic Agents
Exercise physiology
Muscle, Skeletal
Glycogen synthase
Exercise
Leg
omega-N-Methylarginine
business.industry
Skeletal muscle
medicine.disease
Glucose
030104 developmental biology
Endocrinology
Microvessels
Glucose Clamp Technique
biology.protein
Insulin Resistance
Nitric Oxide Synthase
business
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 66
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....369fde60ea16bd39e89dfc476b2d00a4
- Full Text :
- https://doi.org/10.2337/db16-1327