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A study showed that 20-30% of the insulin-like growth factor II/mannose 6-phosphate and transferrin receptors are colocalized with GLUT-4 in GLUT-4-containing vesicles. The finding was derived through a simple method for separating intracellular pools of glucose transporter isoform GLUT-4-containing vesicles from surface sarcolemma and T tubule membranes of rat skeletal muscle cells. Results also showed that insulin stimulation in vivo was succeeded by the translocation of the receptors from their intracellular compartments to the sell surface together with GLUT-4.

Sucrose (Suc) feeding, dexamethasone (Dex) administration and Suc/Dex combination models of insulin resistance were analyzed to determine the level of expression of GLUT-4 glucose transport protein. The degree of expression of GLUT-4 protein depends on the type of model for insulin resistance and the kind of tissue in which the transporter is expressed. Adipocyte insulin resistance is characterized by an increase in basal state GLUT-4 in the plasma membrane. An increase in GLUT-4 expression was exhibited by the skeletal muscle during Dex-induced insulin resistance.

UCP-3 expression in skeletal muscle: effects of exercise, hypoxia, and AMP-activated protein kinase. Am J Physiol Endocrinol Metab 279: E622-E629, 2000.--Uncoupling protein 3 (UCP-3), a member of the mitochondrial transporter superfamily, is expressed primarily in skeletal muscle where it may play a role in altering metabolic function under conditions of fuel depletion caused, for example, by fasting and exercise. Here, we show that treadmill running by rats rapidly (30 min) induces skeletal muscle UCP-3 mRNA expression (sevenfold after 200 min), as do hypoxia and swimming in a comparably rapid and substantial fashion. The expression of the mitochondrial transporters, carnitine palmitoyltransferase 1 and the tricarboxylate carrier, is unaffected under these conditions. Hypoxia and exercise-mediated induction of UCP-3 mRNA result in a corresponding four- to sixfold increase in rat UCP-3 protein. We treated extensor digitorum longus (EDL) muscle with 5'-amino-4-imidazolecarboxamide ribonucleoside (AICAR), a compound that activates AMP-activated protein kinase (AMPK), an enzyme known to be stimulated during exercise and hypoxia. Incubation of rat EDL muscle in vitro for 30 min with 2 mM AICAR causes a threefold increase in UCP-3 mRNA and a 1.5-fold increase of UCP-3 protein compared with untreated muscle. These data are consistent with the notion that activation of AMPK, presumably as a result of fuel depletion, rapidly regulates UCP-3 gene expression. adenosine 5'-monophosphate-activated protein kinase; 5'-amino-4-imidazolecarboxamide ribonucleoside; rats

Zhou, Min, Gino Vallega, Konstantin V. Kandror, and Paul F. Pilch. Insulin-mediated translocation of GLUT-4-containing vesicles is preserved in denervated muscles. Am J Physiol Endocrinol Metab 278: E1019-E1026, 2000.--Skeletal muscle denervation decreases insulin-sensitive glucose uptake into this tissue as a result of marked GLUT-4 protein downregulation (~20% of controls). The process of insulin-stimulated glucose transport in muscle requires the movement or translocation of intracellular GLUT-4-rich vesicles to the cell surface, and it is accompanied by the translocation of several additional vesicular cargo proteins. Thus examining GLUT-4 translocation in muscles from denervated animals allows us to determine whether the loss of a major cargo protein, GLUT-4, affects the insulin-dependent behavior of the remaining cargo proteins. We find no difference, control vs. denervated, in the insulin-dependent translocation of the insulin-responsive aminopeptidase (IRAP) and the receptors for transferrin and insulin-like growth factor II/mannose 6-phosphate, proteins that completely (IRAP) or partially co-localize with GLUT-4. We conclude that 1) denervation of skeletal muscle does not block the specific branch of insulin signaling pathway that connects receptor proximal events to intracellular GLUT-4-vesicles, and 2) normal levels of GLUT-4 protein are not necessary for the structural organization and insulin-sensitive translocation of its cognate intracellular compartment. Muscle denervation also causes a twofold increase in GLUT-1. In normal muscle, all GLUT-1 is present at the cell surface, but in denervated muscle a significant fraction (25.1 [+ or -] 6.1%) of this transporter is found in intracellular vesicles that have the same sedimentation coefficient as GLUT-4-containing vesicles but can be separated from the latter by immunoadsorption. These GLUT-1-containing vesicles respond to insulin and translocate to the cell surface. Thus the formation of insulin-sensitive GLUT-1-containing vesicles in denervated muscle may be a compensatory mechanism for the decreased level of GLUT-4. denervation; rats; skeletal muscle

Studies the insulin-mediated translocation of GLUT-4-containing vesicles in denervated muscle. Translocation to the cell surface in response to insuling; Formationof intracellular GLUT-1-containing vesicles.

Presents information on a study regarding separation procedure on intracellular pool of glucose transporter isoform GLUT-4-containing vesicles from the skeletal muscle cells. Experimental procedures; Results of the muscle membrane fractionation.

Examines the effect of three different models of insulin resistance on the expression of GLUT-4, a glucose transporter, in rat heart, skeletal muscle and adipose tissue. Indication that regulation of GLUT-4 expression is affected by model of insulin resistance and the tissue involved.