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The Biochemical journal
02 11, 2022;479 (3): 445-462.

GLUT4 On the move.

Daniel J Fazakerley, Francoise Koumanov, Geoffrey D Holman
Author Information
  1. Daniel J Fazakerley: Metabolic Research Laboratories, Wellcome-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, U.K.
  2. Francoise Koumanov: Department for Health, Centre for Nutrition, Exercise, and Metabolism, University of Bath, Bath, Somerset BA2 7AY, U.K.
  3. Geoffrey D Holman: Department of Biology and Biochemistry, University of Bath, Bath, Somerset BA2 7AY, U.K. ORCID
PMID: 35147164 DOI: 10.1042/BCJ20210073

Abstract

Insulin rapidly stimulates GLUT4 translocation and glucose transport in fat and muscle cells. Signals from the occupied insulin receptor are translated into downstream signalling changes in serine/threonine kinases within timescales of seconds, and this is followed by delivery and accumulation of the glucose transporter GLUT4 at the plasma membrane. Kinetic studies have led to realisation that there are distinct phases of this stimulation by insulin. There is a rapid initial burst of GLUT4 delivered to the cell surface from a subcellular reservoir compartment and this is followed by a steady-state level of continuing stimulation in which GLUT4 recycles through a large itinerary of subcellular locations. Here, we provide an overview of the phases of insulin stimulation of GLUT4 translocation and the molecules that are currently considered to activate these trafficking steps. Furthermore, we suggest how use of new experimental approaches together with phospho-proteomic data may help to further identify mechanisms for activation of these trafficking processes.

Keywords

GLUT4 glucose transport insulin membrane traffic membrane trafficking kinetics signal transduction

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Grants

  1. MR/J003417/1/Medical Research Council
  2. MR/S007091/1/Medical Research Council
  3. MR/P002927/1/Medical Research Council

MeSH Term

Adipocytes
Animals
Cell Membrane
Glucose
Glucose Transporter Type 4
Humans
Insulin
Models, Biological
Muscle Cells
Phosphorylation
Protein Processing, Post-Translational
Protein Transport
Signal Transduction
Subcellular Fractions

Chemicals

Glucose Transporter Type 4
Insulin
Glucose
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 3

Word Cloud

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