A peroxovanadium compound stimulates muscle glucose transport as powerfully as insulin and contractions combined

Lorraine A Nolte1, Dong-Ho Han, Polly A Hansen

  • 1Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.

Diabetes
|July 29, 2003
PubMed

Insights

A novel compound, bis-peroxovanadium,1,10-phenanthrolene (bpV(phen)), significantly boosts glucose transport and GLUT4 translocation, mimicking maximal insulin and contraction effects. This suggests a powerful IRS-PI 3-K pathway activation can engage contraction-specific GLUT4 vesicles.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Metabolic Regulation

Background:

  • Insulin signaling, involving tyrosine phosphorylation of the insulin receptor (IR) and IR substrates (IRSs), stimulates glucose transport.
  • Muscle contractions independently stimulate glucose transport, suggesting distinct signaling pathways.
  • Peroxovanadates, like bis-peroxovanadium,1,10-phenanthrolene (bpV(phen)), inhibit tyrosine phosphatases, enhancing IRS tyrosine phosphorylation.

Purpose of the Study:

  • To investigate the effect of bpV(phen) on glucose transport and GLUT4 translocation.
  • To determine if bpV(phen) activates both insulin- and contraction-stimulated pathways.
  • To elucidate the role of the IRS-PI 3-K signaling pathway in bpV(phen)-mediated glucose uptake.

Main Methods:

  • Treatment of cells with bpV(phen), insulin, and/or muscle contractions.
  • Assessment of glucose transport and GLUT4 translocation.
  • Inhibition of phosphatidylinositol 3-kinase (PI 3-K) using wortmannin and LY294002.
  • Measurement of IRS-PI 3-K pathway activation.

Main Results:

  • bpV(phen) stimulated glucose transport and GLUT4 translocation comparable to maximal insulin and contraction.
  • bpV(phen)-induced effects were completely blocked by PI 3-K inhibitors.
  • The combined effect of bpV(phen) and contractions did not exceed bpV(phen) alone.
  • IRS-PI 3-K pathway activation was significantly higher with bpV(phen) than with insulin.

Conclusions:

  • bpV(phen) powerfully activates the IRS-PI 3-K signaling pathway.
  • This potent activation allows GLUT4 vesicles, typically responsive to contractions, to be translocated.
  • The findings highlight the potential of targeting the IRS-PI 3-K pathway to enhance glucose uptake, particularly in conditions where insulin signaling is impaired.

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