Neomycin prevents the wortmannin inhibition of insulin-stimulated Glut4 translocation and glucose transport in 3T3-L1 adipocytes.
Insulin stimulates the movement of the facilitative glucose transporter glucose transporter-4 (Glut4) from an intracellular compartment to the plasma membrane in adipocytes and muscle cells, resulting in an increased rate of glucose uptake. Insulin-stimulated Glut4 translocation and glucose transport are abolished by wortmannin, a specific inhibitor of phosphatidylinositol 3'-kinase (PI3K). Here, we demonstrate that neomycin, a drug that masks the cellular substrate of PI3K, phosphatidylinositol 4,5-bisphosphate (PIP), prevents wortmannin inhibition of insulin-stimulated (2)Glut4 translocation and glucose transport without activating protein kinase B, a downstream effector of PI3K. These results suggest that PIP(2) may have an important regulatory function in insulin-stimulated Glut4 translocation and glucose transport.
James
Declan J
DJ
Henry Welcome Laboratory of Cell Biology, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, Davidson Building, University of Glasgow, Glasgow G12 8QQ, Scotland, UK.
Salaün
Christine
C
Brandie
Fiona M
FM
Connell
John M C
JM
Chamberlain
Luke H
LH
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000730:Androstadienes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D009355:Neomycin / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D000077191:Wortmannin
D000730:Androstadienes; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495693:Slc2a4 protein, mouse; D009355:Neomycin; D000077191:Wortmannin