Regulation of Glucose Transporters and the Na/K-ATPase by Insulin in Skeletal Muscle
In addition to its functional role of conferring bodily movement, skeletal muscle, by virtue of its total body mass also plays a key role affecting whole body metabolism. Skeletal muscle represents the chief storage site for protein (in the form of free amino acid pools and contractile muscle protein) (Rennie, 1985) and inorganic ions, notably potassium (Bergstrom et al, 1981). In the post-prandial state muscle represents the principal tissue responsible for insulin-stimulated glucose utilization (for oxidative metabolism and/or glycogen synthesis) (DeFronzo et al, 1981) and is a significant contributor in the inter-organ flow of carbon and nitrogen (in the form of muscle alanine and glutamine efflux) (Hundal, 1991). The ability to store or exclude organic and inorganic nutrients against a concentration gradient is maintained through the activity of specific membrane transport proteins as well as the selective permeability properties of the membrane. In skeletal muscle, a primary insulin target, the activation of glucose transport and Na/K transport (mediated by the Na pump or its enzymic equivalent the Na/K-ATPase) represent two of the best documented responses to the hormone (Klip et al, 1987; Klip and Paquet, 1990; Hirshman et al, 1990; Marette et al, 1992a; Erlij and Grinstein, 1976; Clausen and Kohn, 1977). The present chapter reviews work from our laboratory which has focused on the molecular basis by which insulin activates glucose transport and the Na/K-ATPase in skeletal muscle and the possible implications that regulation of these membrane processes may have during non-insulin dependent diabetes mellitus (NIDDM).
KeywordsSkeletal Muscle Human Skeletal Muscle GLUT4 Glucose Transporter Muscle Glucose Uptake Transverse Tubule
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