Skeletal muscle microvascular blood flow and insulin action

M.A. Keske, Institute for Physical Activity and Nutrition (IPAN), Deakin University, Burwood, VIC 3125, Australia.

Skeletal muscle is an important site for insulin-mediated glucose disposal in the post-prandial state (Keske et al., 2009). The classical action of insulin to increase muscle glucose uptake involves insulin binding to receptors on myocytes to stimulate the insulin signalling pathway leading to GLUT4 translocation to the cell surface membrane, enhancing glucose uptake. However, an additional role of insulin on muscle glucose uptake is its action to increase muscle blood flow thereby improving insulin and glucose delivery to myocytes. Insulin can increase large blood vessel (e.g. total limb blood flow) as well as small blood vessel (e.g. microvascular) blood flow (Vincent et al., 2004; Premilovac et al., 2014). However, insulin-mediated glucose uptake is modified by microvascular blood flow and not total limb blood flow (Vincent et al., 2004). This microvascular action of insulin is mediated, at least in part, by nitric oxide synthase (Vincent et al., 2004; Kubota et al., 2011) and accounts for 40-50% of insulin-stimulated glucose disposal in skeletal muscle (Vincent et al., 2004). Skeletal muscle microvascular blood flow is impaired during insulin resistance (Premilovac et al., 2014; Kubota et al., 2011) and type 2 diabetes (Russell et al., 2017). There is a growing body of literature suggesting that impairments in microvascular insulin action have important physiological consequences in the early pathogenesis of insulin resistance and can precede myocyte insulin resistance (Premilovac et al., 2014; Kubota et al., 2011; Bonner et al., 2013). Therefore, interventions targeting the microcirculation in skeletal muscle is a novel approach to improve glucose homeostasis in insulin resistant states (Premilovac et al., 2014; Russell et al., 2017).

Bonner JS, Lantier L, Hasenour CM, James FD, Bracy DP, Wasserman DH. (2013). Diabetes 62, 572-80.

Keske MA, Clerk LH, Price WJ, Jahn LA, Barrett EJ. (2009). Diabetes Care 32, 1672-7.

Kubota T, Kubota N, Kumagai H, Yamaguchi S, Kozono H, Takahashi T, Inoue M, et al. (2011). Cell Metab 13, 294-307.

Premilovac D1, Richards SM, Rattigan S, Keske MA. (2014) Diabetologia 57, 2586-95.

Russell RD, Hu D1, Greenaway T, Blackwood SJ, Dwyer RM, Sharman JE, Jones G, et al. (2017). Diabetes Care 40, 1256-1263.

Vincent MA, Clerk LH, Lindner JR, Klibanov AL, Clark MG, Rattigan S, Barrett EJ. (2004) Diabetes 53, 1418-23.