GLUT4 translocation: the last 200 nanometers

Cell Signal. 2007 Nov;19(11):2209-17. doi: 10.1016/j.cellsig.2007.06.003. Epub 2007 Jun 21.

Abstract

Insulin regulates circulating glucose levels by suppressing hepatic glucose production and increasing glucose transport into muscle and adipose tissues. Defects in these processes are associated with elevated vascular glucose levels and can lead to increased risk for the development of Type 2 diabetes mellitus and its associated disease complications. At the cellular level, insulin stimulates glucose uptake by inducing the translocation of the glucose transporter 4 (GLUT4) from intracellular storage sites to the plasma membrane, where the transporter facilitates the diffusion of glucose into striated muscle and adipocytes. Although the immediate downstream molecules that function proximal to the activated insulin receptor have been relatively well-characterized, it remains unknown how the distal insulin-signaling cascade interfaces with and recruits GLUT4 to the cell surface. New biochemical assays and imaging techniques, however, have focused attention on the plasma membrane as a potential target of insulin action leading to GLUT4 translocation. Indeed, it now appears that insulin specifically regulates the docking and/or fusion of GLUT4-vesicles with the plasma membrane. Future work will focus on identifying the key insulin targets that regulate the GLUT4 docking/fusion processes.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Transport / drug effects
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cytoplasmic Vesicles / drug effects
  • Cytoplasmic Vesicles / metabolism
  • Glucose / metabolism
  • Glucose Transporter Type 4 / metabolism*
  • Humans
  • Insulin / pharmacology

Substances

  • Glucose Transporter Type 4
  • Insulin
  • Glucose