Regulation of skeletal muscle glucose uptake during contraction/ exercise by nitric oxide (NO)/ neuronal nitric oxide synthase MU (NOSμ)
During exercise/ muscle contraction, large amounts of blood glucose are taken up into skeletal muscle fibers thus removing glucose from the bloodstream. This process is regulated differently to insulin-stimulated muscle glucose uptake and is normal in humans with type 2 diabetes (T2D) and in diabetic rodent models. A number of candidates have been implicated to play a role in the regulation of skeletal muscle glucose uptake during contraction and it is likely that there is some redundancy. In humans, there is convincing evidence that nitric oxide (NO) plays a role in contraction-stimulated muscle glucose uptake and may be promising from a therapeutic standpoint for people with T2D since they have a greater reliance on NO-mediated glucose uptake during exercise. However, evidence for a role of NO in regulating contraction-stimulated muscle glucose uptake in rodents is conflicting, most likely due to methodological inconsistencies. Studies have almost entirely involved the use of NO synthase (NOS) inhibitors with little data in genetically-modified models examining the role of NO in contraction-stimulated glucose uptake. Neuronal NOSμ is the major NOS isoform that activates the NO/ cGMP downstream signalling during skeletal muscle contraction. In this thesis, the role of NO/ nNOSμ in the regulation of skeletal muscle glucose uptake was examined. In rodents, NO/ nNOSμ is also involved in the regulation of skeletal muscle blood flow during contraction/ exercise, and glucose uptake is influenced by blood flow and glucose delivery. Therefore, mice lacking nNOSμ were used to investigate its role in glucose uptake during both ex vivo contraction and more physiological in vivo treadmill exercise. Also, a T2D rat model was generated and used to investigate if diabetic rats have a greater reliance on NO-mediated muscle glucose uptake during in situ contraction, as has previously been shown during exercise in people with T2D.
1101 Medical Biochemistry and Metabolomics, 1106 Human Movement and Sports Science, Institute of Sport, Exercise and Active Living (ISEAL), College of Health and Biomedicine
Networked Digital Library of Theses and Dissertations