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

Abstract

Voluntary wheel running (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 μIU/mL), were assessed in second order arterioles (2A) from the white (Gw) and red (Gr) gastrocnemius of sedentary 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 12–20 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.

Endurance, interval sprint, and resistance exercise training: impact on microvascular dysfunction in type 2 diabetes

“…Thus EX-induced microvascular adaptations in the setting of T2D differ between training modalities and among skeletal muscle arterioles. Interestingly, similar training-and arterial-dependent differences have been observed with regard to microvascular insulin signaling in T2D (34,36,101,102).…”

“…3C) (95). Thus EX-induced improvements in EDD are distributed heterogeneously throughout skeletal muscle arteriolar networks, and the pattern of distribution of these effects depends on types of training and signal for EDD (i.e., ACh vs. insulin) (95,102). These observations add importantly to the growing body of evidence that highlight differences among vasomotor properties of arteries of different tissues (89), within tissue (8,41,79,89,135,136,151), and along the length of the arterial network (39,46,58,73,77,78,81,83).…”

“…In line with the aforementioned findings, results from our laboratory indicate that improvements in EDD produced by EX in skeletal muscle arterioles from T2D rats are dependent on skeletal muscle fiber recruitment during the exercise bouts. Specifically, we established that insulin signaling in arteriolar endothelium differs among types of skeletal muscle among different branch orders in skeletal muscle arteriolar trees (14,64,95) and that different types of EX (wheel running, endurance, and interval sprint training performed on a treadmill) impact the arterioles differentially and improve insulin-induced EDD nonuniformly in the arterial tree of skeletal muscle (14,95,101,102). Insulinmediated vasodilation was improved by wheel running and vigorous interval sprint training in G2A-W (Fig.…”

“…These effects may be potentiated by increasing capillary blood flow in previously perfused and underperfused capillaries. Therefore, in patients with insulin resistance or T2D, from a vascular perspective, EX may improve insulin signaling by enhancing microvascular responses to insulin (36,62,95,101,102,115), attenuating microvascular rarefaction (Fig. 4, A-D) (23,67,126) and augmenting capillary blood flow (59,118,119), all of which will augment perfusion and increase glucose and insulin delivery in skeletal muscle (21).…”

“…Importantly, each of the aforementioned conditions (neuropathy, retinopathy, nephropathy, exercise intolerance, and glucose intolerance) is caused, in part, by microvascular dysfunction. Studies performed in humans with insulin resistance or T2D and in animal models of disease demonstrate that EX mediates local and systemic improvements in endothelial (14,27,28,93,95,(101)(102)(103) and smooth muscle function (14,27,95) indicated by improved vasodilator signaling. Exercise training also appears to attenuate microvascular rarefaction in skeletal muscle associated with insulin resistance (23,52,67,90,126).…”