Evidence that nitric oxide increases glucose transport in skeletal muscle

Abstract

Nitric oxide synthase (NOS) is expressed in skeletal muscle. However, the role of nitric oxide (NO) in glucose transport in this tissue remains unclear. To determine the role of NO in modulating glucose transport, 2-deoxyglucose (2-DG) transport was measured in rat extensor digitorum longus (EDL) muscles that were exposed to either a maximally stimulating concentration of insulin or to an electrical stimulation protocol, in the presence of NG-monomethyl-L-arginine, a NOS inhibitor. In addition, EDL preparations were exposed to sodium nitroprusside (SNP), an NO donor, in the presence of submaximal and maximally stimulating concentrations of insulin. NOS inhibition reduced both basal and exercise-enhanced 2-DG transport but had no effect on insulin-stimulated 2-DG transport. Furthermore, SNP increased 2-DG transport in a dose-responsive manner. The effects of SNP and insulin on 2-DG transport were additive when insulin was present in physiological but not in pharmacological concentrations. Chronic treadmill training increased protein expression of both type I and type III NOS in soleus muscle homogenates. Our results suggest that NO may be a potential mediator of exercise-induced glucose transport.

Effects of the nitric oxide donor, sodium nitroprusside, on resting leg glucose uptake in patients with type 2 diabetes

“…Similarly, methacholine increased leg glucose uptake [38], but it was assumed that such effects were a consequence of NO-mediated endothelial-dependent vasodilation and increased glucose delivery. Consistent with animal data [13,[16][17][18][19]29] the current study suggests that SNP increased glucose uptake beyond the effects on blood flow via increasing translocation of the SLC2A4 glucose transporter.…”

“…SNP increases glucose transport in a number of cell culture models including human peripheral blood mononuclear cells [24], 3T3-L1 adipocytes [25], L929 fibroblasts [26], isolated rat cardiomyocytes [27] and human vascular smooth muscle cells [28]. SNP also increases glucose transport in isolated rat skeletal muscle preparations [13,[16][17][18][19]. The fact that SNP is able to increase glucose uptake in both cell culture and isolated muscle preparations suggests that NO has a direct action on glucose transport via SLC2A4 translocation, in addition to increasing glucose delivery via effects on blood flow.…”

“…While the insulin pathway involves insulin binding to its receptor inducing tyrosine kinase activity, phosphorylation of insulin receptor substrate proteins with subsequent activation of phosphatidylinositol-3-kinase [6], the contraction pathway, is independent of these steps [7][8][9]. A number of molecules including calcium [5,10], protein kinase C [5], AMP-activated protein kinase (AMPK) [11], bradykinin [12] and NO [13] have been implicated in contractionmediated glucose uptake.…”

“…Electrical stimulation, eliciting muscle contraction causes release of NO [15]. Animal studies have demonstrated that NO donor drugs such as sodium nitroprusside (SNP) increase glucose transport in skeletal muscle [13,[16][17][18][19]. SNP also increases SLC2A4 translocation in isolated rat skeletal muscle preparations [16].…”

nNOS regulation of skeletal muscle fatigue and exercise performance

“…nNOSμ expression and activity increased in the hindlimb and respiratory muscles of rats subjected to long-term treadmill running or swimming (Balon and Nadler 1997;TatchumTalom et al 2000;Vassilakopoulos et al 2003). Skeletal muscle nNOSμ expression declines with age in rats, suggesting that sarcopenia may be linked with the downregulation of nNOSμ (Song et al 2009), but long-term treadmill running has been found to reverse this age-related decrease in nNOSμ expression (Song et al 2009).…”