Role of nitric oxide in skeletal muscle glucose uptake during exercise

Abstract

New Findings r What is the topic of this review?Is nitric oxide (NO) important in mediating skeletal muscle glucose uptake during contraction/exercise? r What advances does it highlight?Nitric oxide appears essential for skeletal muscle glucose uptake during contraction/exercise. Nitric oxide is produced within skeletal muscle fibres and has various functions in skeletal muscle. There is evidence that NO may be essential for normal increases in skeletal muscle glucose uptake during contraction/exercise. Although there have been some discrepant results, it has been consistently demonstrated that inhibition of NO synthase (NOS) attenuates the increase in skeletal muscle glucose uptake during contraction in mouse and rat muscle ex vivo, during in situ contraction in rats and during exercise in humans. The NO-mediated increase in skeletal muscle glucose uptake during contraction/exercise is probably due to the modulation of intramuscular signalling that ultimately increases glucose transporter 4 (GLUT4) translocation and is, surprisingly, independent of blood flow. In this review, we discuss the evidence for and against a role of NO in regulating skeletal muscle glucose uptake during contraction/exercise and outline the possible mechanism(s) involved. Emerging findings regarding the role of neuronal NOS mu (nNOSµ) in this process are also discussed.

l -arginine ingestion inhibits eccentric contraction-induced proteolysis and force deficit via S -nitrosylation of calpain

“…In skeletal muscles, nitric oxide (NO), which is synthesized from L-arginine (ARG) primarily by neuronal NO synthase (NOS), is moderately generated in the resting state, and its production increases markedly with contractile activity (Stamler and Meissner 2001;Wray et al 2011;Hong et al 2014;Dyakova et al 2015). Modest and transient increases in NO play essential roles in the normal cellular signaling ).…”

Novel regulatory mechanisms in muscle metabolism during exercise

“…The molecular mechanisms that lead to increased muscle NOS activity and NO production during exercise and downstream signalling that results in increased muscle glucose uptake are not understood. In the review by Hong et al (2014), the effect of NO on glucose uptake in muscle during exercise is discussed. They conclude that current evidence suggests that NO plays an important role in skeletal muscle glucose uptake during contraction/exercise; however, the source of the NO and the downstream mechanisms involved are still mostly unresolved.…”

“…In the review by Hong et al . (), the effect of NO on glucose uptake in muscle during exercise is discussed. They conclude that current evidence suggests that NO plays an important role in skeletal muscle glucose uptake during contraction/exercise; however, the source of the NO and the downstream mechanisms involved are still mostly unresolved.…”

Enhanced external counterpulsation (EECP) improves biomarkers of glycemic control in patients with non-insulin-dependent type II diabetes mellitus for up to 3 months following treatment

“…The insulin-mediated pathway is profoundly impaired in T2DM, while the contractionmediated glucose uptake pathway is preserved [10]. In patients with T2DM, the NO-mediated glucose uptake pathway becomes increasingly important and there is increased reliance on NO cell signaling [8,9]. Therefore, therapies designed to upregulate endogenous NO bioavailability may be beneficial to T2DM patients.…”

“…Alternative treatments such as dipeptidyl peptidase-4 (DPP-4) inhibitors [4] and insulin glargine with neutral protamine Hagedorn (NPH) insulin [5] have been utilized, but alternative treatments for T2DM should continue to be explored. Skeletal muscle glucose uptake involves 3 distinct pathways: (1) insulin-mediated glucose uptake [6], (2) contraction-mediated glucose uptake [7], and (3) nitric oxide (NO)-mediated glucose uptake [8,9]. The insulin-mediated pathway is profoundly impaired in T2DM, while the contractionmediated glucose uptake pathway is preserved [10].…”