Muscle Contraction, but Not Insulin, Increases Microvascular Blood Volume in the Presence of Free Fatty Acid–Induced Insulin Resistance
Open Access
- 12 August 2009
- journal article
- Published by American Diabetes Association in Diabetes
- Vol. 58 (11), 2457-2463
- https://doi.org/10.2337/db08-1077
Abstract
OBJECTIVE: Insulin and contraction each increase muscle microvascular blood volume (MBV) and glucose uptake. Inhibiting nitric oxide synthase blocks insulin's but not contraction's effects. We examined whether contraction could augment the MBV increase seen with physiologic hyperinsulinemia and whether free fatty acid (FFA)-induced insulin resistance differentially affects contraction- versus insulin-mediated increases in MBV. RESEARCH DESIGN AND METHODS: Rats were fasted overnight. Plasma FFAs were increased by intralipid/heparin infusion (3 h), insulin was increased with a euglycemic clamp (3 mU · min−1 · kg−1), and hindlimb muscle contraction was electrically stimulated. Muscle MBV was measured using contrast-enhanced ultrasound. Insulin transport into muscle was measured using 125I-insulin. BQ-123 (0.4 mg/h) was used to block the endothelin-1 (ET-1) receptor A. RESULTS: Superimposing contraction on physiologic hyperinsulinemia increased MBV within 10 min by 37 and 67% for 0.1 or 1 Hz, respectively (P < 0.01). FFA elevation alone did not affect MBV, whereas 0.1 Hz stimulation doubled MBV (P < 0.05) and increased muscle insulin uptake (P < 0.05) despite high FFA. Physiologic hyperinsulinemia during FFA elevation paradoxically decreased MBV (P < 0.05). This MBV decrease was reversed by either 0.1 Hz contraction or ET-1 receptor A antagonism, and the combination raised MBV above basal. CONCLUSIONS: Contraction recruits microvasculature beyond that seen with physiologic hyperinsulinemia by a distinct mechanism that is not blocked by FFA-induced vascular insulin resistance. The paradoxical MBV decline seen with insulin plus FFA may result from differential inhibition of insulin-stimulated nitric oxide–dependent vasodilation relative to ET-1 vasoconstriction. Our results implicate ET-1 as a potential mediator of FFA-induced vascular insulin resistance.Keywords
This publication has 47 references indexed in Scilit:
- Insulin Signaling Stimulates Insulin Transport by Bovine Aortic Endothelial CellsDiabetes, 2008
- Contraction Stimulates Nitric Oxide–Independent Microvascular Recruitment and Increases Muscle Insulin UptakeDiabetes, 2007
- Effect of acute hyperlipidemia on autonomic and cardiovascular control in humansJournal of Applied Physiology, 2007
- Reciprocal relationships between abnormal metabolic parameters and endothelial dysfunctionCurrent Opinion in Lipidology, 2007
- Reduced Access to Insulin-Sensitive Tissues in Dogs With Obesity Secondary to Increased Fat IntakeDiabetes, 2006
- Molecular mechanisms of lipid‐induced insulin resistance in muscle, liver and vasculatureDiabetes, Obesity and Metabolism, 2004
- Skeletal muscle contraction stimulates capillary recruitment and glucose uptake in insulin-resistant obese Zucker ratsAmerican Journal of Physiology-Endocrinology and Metabolism, 2004
- FFA-Induced Endothelial Dysfunction Can Be Corrected by Vitamin CJournal of Clinical Endocrinology & Metabolism, 2002
- Impaired free fatty acid utilization by skeletal muscle in non-insulin-dependent diabetes mellitus.JCI Insight, 1994
- Insulin transport across capillaries is rate limiting for insulin action in dogs.JCI Insight, 1989