Neomycin prevents the wortmannin inhibition of insulin-stimulated Glut4 translocation and glucose transport in 3T3-L1 adipocytes

J Biol Chem. 2004 May 14;279(20):20567-70. doi: 10.1074/jbc.C400096200. Epub 2004 Mar 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adipocytes / drug effects
  • Adipocytes / metabolism*
  • Androstadienes / antagonists & inhibitors
  • Androstadienes / pharmacology*
  • Animals
  • Glucose Transporter Type 4
  • Insulin / metabolism*
  • Insulin Secretion
  • Mice
  • Monosaccharide Transport Proteins / metabolism*
  • Muscle Proteins*
  • Neomycin / pharmacology*
  • Protein Transport / drug effects
  • Wortmannin

Substances

  • Androstadienes
  • Glucose Transporter Type 4
  • Insulin
  • Monosaccharide Transport Proteins
  • Muscle Proteins
  • Slc2a4 protein, mouse
  • Neomycin
  • Wortmannin