Glucose transporter GLUT4 (also known as SLC2A4) plays a major role in glucose homeostasis and is efficiently retained intracellularly in adipocytes and myocytes. To simplify the analysis of its retention, here, various intracellular GLUT4 domains were fused individually to reporter molecules. Of the four short cytoplasmic loops of GLUT4, only the first nine-residue-long loop conferred intracel...

In several cell types, specific membrane proteins are retained intracellularly and rapidly redistributed to the surface in response to stimulation. In fat and muscle, the GLUT4 glucose transporter is dynamically retained because it is rapidly internalized and slowly recycled to the plasma membrane. Insulin increases the recycling of GLUT4, resulting in a net translocation to the surface. We hav...

After a meal, insulin lowers blood glucose levels by stimulating the sugar's uptake into muscle and fat cells via the glucose transporter GLUT4. Insulin promotes GLUT4's translocation to the cell surface, a process that goes awry in patients with type II diabetes and which depends, in part, on the small GTPase RAB10. Bruno and Brumfield et al. reveal that RAB10 works with SEC16A—a protein invol...

Glucose transporter 4 (GLUT4) moves from perinuclear storage regions to the plasma membrane in response to insulin and facilitates glucose uptake. This MQP examined the roles of three proteins (GAPDH, PGK, and PGAM) in glucose uptake and GLUT4 trafficking in 3T3-L1 adipocytes by performing glucose uptake assays on adipocytes in which these proteins were selectively knocked down using RNAi. GLUT...

Insulin resistance is instrumental in the pathogenesis of type 2 diabetes mellitus and the Insulin Resistance Syndrome. While insulin resistance involves decreased glucose transport activity in skeletal muscle, its molecular basis is unknown. Since muscle GLUT4 glucose transporter levels are normal in type 2 diabetes, we have tested the hypothesis that insulin resistance is due to impaired tran...

Insulin rapidly represses expression of the gene encoding the insulin-responsive glucose transporter (GLUT4) in 3T3-L1 mouse adipocytes. Upon exposure to the hormone the cellular level of GLUT4 mRNA falls (t1/2 approximately 2.5 hr) to 20-30% of its initial level within 10 hr. This is followed by a similar decrease in the level of GLUT4 protein. Down-regulation of GLUT4 mRNA is a result of both...

GLUT4 has long been known to be an insulin responsive glucose transporter. Regulation of GLUT4 has been a major focus of research on the cause and prevention of type 2 diabetes. Understanding how insulin signaling alters the intracellular trafficking of GLUT4 as well as understanding the fate of glucose transported into the cell by GLUT4 will be critically important for seeking solutions to the...

Insulin-stimulated glucose uptake requires the activation of several signaling pathways to mediate the translocation and fusion of GLUT4 vesicles from an intracellular pool to the plasma membrane. The studies presented here show that inhibition of myosin II activity impairs GLUT4-mediated glucose uptake but not GLUT4 translocation to the plasma membrane. We also show that adipocytes express bot...

A major consequence of insulin binding its receptor on fat and muscle cells is translocation of the facilitative glucose transporter GLUT4 from an intracellular store to the cell surface where it serves to clear glucose from the bloodstream. Sorting of GLUT4 into its insulin-sensitive store requires the GGA [Golgi-localized, γ-ear-containing, ADP ribosylation factor (ARF)-binding] adaptor prote...

To investigate the cellular and subcellular distribution of glucose transporters in skeletal muscle, the glucose transporter isoform GLUT4 was localized in human muscle by electron microscopy via immunogold labeling with monoclonal (1F8) or COOH-terminal peptide polyclonal (ECU4) antibody and in isolated rat membranes by Western blot. There was no labeling of GLUT4 in endothelial cells of the c...