Abstract
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.
Highlights
Neomycin Prevents the Wortmannin Inhibition of stimulated glucose transporter-4 (Glut4) translocation to the cell surface requires the co-ordinated activity of numerous intracellular target molecules [3]
We demonstrate that neomycin, a drug that masks the cellular substrate of phosphatidylinositol 3-kinase (PI3K), phosphatidylinositol 4,5-bisphosphate (PIP2), prevents wortmannin inhibition of insulin-stimulated Glut4 translocation and glucose transport without activating protein kinase B, a downstream effector of PI3K
Neomycin Restores the Insulin-stimulated Glucose Transport Inhibited by the PI3K Inhibitor Wortmannin—To analyze the possible role of PIP2 in insulin-stimulated glucose transport, we examined the effect of the aminoglycoside, neomycin, on glucose transport into 3T3-L1 adipocytes
Summary
Neomycin Prevents the Wortmannin Inhibition of stimulated Glut translocation to the cell surface requires the co-ordinated activity of numerous intracellular target molecules [3]. Insulin-stimulated Glut translocation and glucose transport are abolished by wortmannin, a specific inhibitor of phosphatidylinositol 3kinase (PI3K). We demonstrate that neomycin, a drug that masks the cellular substrate of PI3K, phosphatidylinositol 4,5-bisphosphate (PIP2), prevents wortmannin inhibition of insulin-stimulated Glut translocation and glucose transport without activating protein kinase B, a downstream effector of PI3K. These results suggest that PIP2 may have an important regulatory function in insulin-stimulated Glut translocation and glucose transport. Recent work by the groups of Saltiel and Pessin [11, 12] have identified several components of a PI3K-independent signaling pathway required for insulin-stimulated glucose transport; these components include CAP, c-Cbl, and the small GTPase, TC10
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