Voluntary Wheel Running Selectively Augments Insulin-Stimulated Vasodilation in Arterioles from White Skeletal Muscle of Insulin-Resistant Rats

Background: Exercise (RUN) prevents declines in insulin-mediated vasodilation, an important component of insulin-mediated glucose disposal, in rats prone to obesity and insulin resistance. Objective: Determine whether RUN (1) improves insulin-stimulated vasodilation after insulin resistance has been established, and (2) differentially affects arterioles from red and white muscle. Methods: Insulin signaling and vasoreactivity to insulin (1-1000 mu IU/mL) were assessed in 2A from the Gw and Gr of SED OLETF rats at 12 and 20 weeks of age (SED12, SED20) and those undergoing RUN (RUN20) or caloric restriction (CR20; to match body weight of RUN) from 12 to 20 weeks. Results: Glucose and insulin responses to i.p. glucose were reduced in RUN20, elevated in SED20 (p < 0.05 vs. SED12), and maintained in CR20. Insulin-stimulated vasodilation was greater in Gw but not Gr, 2As of RUN20 (p < 0.01 vs. all groups), and was improved by ET-1 receptor inhibition in Gw 2As from SED20 and CR20 (p < 0.05). There were no differences in microvascular insulin signaling among groups or muscle beds. Conclusions: RUN selectively improved insulin-mediated vasodilation in Gw 2As, in part through attenuated ET-1 sensitivity/production, an adaptation that was independent of changes in adiposity and may contribute to enhanced insulin-stimulated glucose disposal.