Insulin stimulates fusion, but not tethering, of GLUT4 vesicles in skeletal muscle of HA-GLUT4-GFP transgenic mice.

Insulin regulates glucose uptake into fat and muscle by modulating the subcellular distribution of GLUT4 between the cell surface and intracellular compartments. However, quantification of these translocation processes in muscle by classical subcellular fractionation techniques is confounded by contaminating microfibrillar protein; dynamic studies at the molecular level are almost impossible. In this study, we introduce a muscle-specific transgenic mouse model in which HA-GLUT4-GFP is expressed under the control of the MCK promoter.

Identification and characterization of p49/STRAP as a novel GLUT4-binding protein.

To identify novel regulatory components involved in the recycling of the insulin-responsive glucose transporter GLUT4, we have used the yeast two-hybrid system to isolate GLUT4-binding proteins from a rat adipose cell cDNA library. We found a 49-kDa protein (p49/STRAP) that specifically interacts with an acidic amino acid motif (Q7IGSEDG) in the N-terminus of GLUT4. Confocal immunofluorescence microscopy of primary rat adipose cells shows co-localization of myc-p49 with GLUT4 and also with the ER-resident protein calnexin.

7-hydroxystaurosporine (UCN-01) inhibition of Akt Thr308 but not Ser473 phosphorylation: a basis for decreased insulin-stimulated glucose transport.

7-hydroxystaurosporine (UCN-01) infused for 72 hours by continuous i.v. infusion induced insulin resistance during phase I clinical trials.