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Phenylarsine oxide inhibits insulin activation of phosphatidylinositol 3'-kinase

Y P Han1, R A Kohanski

  • 1Department of Biochemistry, Mount Sinai School of Medicine, New York, New York 10029, USA.

Biochemical and Biophysical Research Communications
|November 5, 1997
PubMed

Insights

Phenylarsine oxide (PAO) inhibits phosphatidylinositol 3'-kinase (PI3'-K) activation, a key step in insulin-stimulated glucose transport. This study identifies PI3'-K as a PAO-sensitive target in the insulin signaling pathway.

Area of Science:

  • Cell biology
  • Biochemistry
  • Metabolic signaling

Background:

  • Insulin receptor autophosphorylation triggers glucose transport in adipocytes via insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3 -kinase (PI3 -K).
  • Phenylarsine oxide (PAO) inhibits glucose transport but its specific molecular target remains unidentified.

Purpose of the Study:

  • To investigate the effect of PAO on early insulin signaling events, specifically PI3 -K activation.
  • To identify the PAO-sensitive target within the insulin signaling pathway.

Main Methods:

  • Utilized 3T3-L1 adipocytes to study insulin signaling.
  • Assessed tyrosine phosphorylation of IRS-1 and PI3 -K recruitment to IRS-1 following insulin stimulation.
  • Evaluated the effect of PAO on PI3 -K activity both in intact cells and in vitro.

Main Results:

  • PAO exposure inhibited PI3 -K activation in 3T3-L1 adipocytes.
  • PAO did not affect IRS-1 tyrosine phosphorylation or PI3 -K recruitment to IRS-1.
  • PAO demonstrated inhibitory effects on PI3 -K activity in in vitro assays.

Conclusions:

  • Phosphatidylinositol 3 -kinase (PI3 -K) is identified as a PAO-sensitive target in the insulin signaling pathway.
  • Inhibition of PI3 -K activation by PAO explains its effect on glucose transport.
  • These findings elucidate a specific molecular mechanism for PAO's action on insulin signaling.

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