Chronic wheel running selectively augments insulin‐stimulated vasodilation in arterioles from the white gastrocnemius

Abstract

Insulin-stimulated vasodilation (ISV) typically accounts for ~40% of insulin-stimulated glucose uptake but is impaired in obesity and insulin resistance (IR) due to an imbalance in endothelium-derived nitric oxide and endothelin-1 (ET-1). To determine whether voluntary wheel running (RUN): 1) restores ISV after the development of IR and 2) differentially impacts ISV in second order arterioles (2A) from white (Gw) and red gastrocnemius (Gr), we randomized sedentary 12 wk OLETF rats (SED12) prone to hyperphagia-induced obesity/IR to: 1) SED12; 2) SED, 20 wk (SED20); 3) RUN 12–20 wk (RUN20); or 4) caloric restriction 12–20 wk, weight-matched to RUN (CR20). Glucose and insulin responses to an ip glucose tolerance test were reduced in RUN20, maintained in CR20, and elevated in SED20 (P<0.05 vs. SED12). Cytochrome c declined in heart, Gr and Gw of SED20 and CR20 and was maintained in heart and Gr but not Gw of RUN20. ISV was greater in Gw 2As but not Gr 2As of RUN20 (P<0.05 vs. SED12, SED20 and CR20). ET-1 receptor inhibition improved ISV in Gw 2As from SED20 and CR20 (P<0.05). Insulin-stimulated phosphorylation of Akt and eNOS in Gr and Gw 2As did not differ among groups. Thus, despite evidence of training adaptations in Gr but not Gw, RUN improved ISV in Gw 2As, an effect which may be mediated by attenuated sensitivity to ET-1 and may contribute to greater insulin-mediated glucose disposal. Support: NIH HL36088, AHA, VHA, MU iCATS.