The first luminal loop confers insulin responsiveness to glucose transporter 4

Mol Biol Cell. 2012 Mar;23(5):910-7. doi: 10.1091/mbc.E11-10-0839. Epub 2012 Jan 19.

Abstract

Glucose transporter isoform 4 (GLUT4), is the sole glucose transporter responsible for the effect of insulin on postprandial blood glucose clearance. However, the nature of the insulin sensitivity of GLUT4 remains unknown. In this study, we replaced the first luminal loop of cellugyrin, a 4-transmembrane protein that does not respond to insulin, with that of GLUT4. The chimera protein is targeted to the intracellular insulin-responsive vesicles and is translocated to the plasma membrane upon insulin stimulation. The faithful targeting of the chimera depends on the expression of the sorting receptor sortilin, which interacts with the unique amino acid residues in the first luminal loop of GLUT4. Thus the first luminal loop may confer insulin responsiveness to the GLUT4 molecule.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adaptor Proteins, Vesicular Transport / chemistry
  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Blood Glucose / drug effects
  • Glucose Transporter Type 4 / chemistry
  • Glucose Transporter Type 4 / genetics
  • Glucose Transporter Type 4 / metabolism*
  • Insulin / pharmacology*
  • Insulin Resistance*
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mutant Chimeric Proteins / chemistry
  • Mutant Chimeric Proteins / genetics
  • Mutant Chimeric Proteins / metabolism
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Synaptogyrins

Substances

  • Adaptor Proteins, Vesicular Transport
  • Blood Glucose
  • Glucose Transporter Type 4
  • Insulin
  • Membrane Proteins
  • Mutant Chimeric Proteins
  • Nerve Tissue Proteins
  • Synaptogyrins
  • sortilin