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Reduction of insulin signalling pathway IRS-1/IRS-2/AKT/mTOR and decrease of epithelial cell proliferation in the

Maitê M Costa1, Natália M Violato, Sebastião R Taboga

  • 1Department of Physical Education, Faculty of Sciences, São Paulo State University-Unesp, Bauru, São Paulo, Brazil.

International Journal of Experimental Pathology
|May 16, 2012
PubMed

Insights

Dexamethasone-induced insulin resistance in rats reduced key insulin signaling proteins (IRS-1/2, AKT, mTOR) in the prostate, correlating with decreased androgen receptor expression and cell proliferation.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cell Biology

Background:

  • Previous studies showed dexamethasone (DEX) induces atrophy in rat ventral prostate epithelial and smooth muscle cells.
  • Insulin signaling pathway proteins are crucial for cell proliferation and development.

Purpose of the Study:

  • To investigate the insulin signaling pathway and epithelial proliferation in the rat ventral prostate under DEX-induced insulin resistance.
  • To correlate these findings with glucocorticoid receptor (GR) and androgen receptor (AR) expression.

Main Methods:

  • Insulin resistance was induced in adult male Wistar rats using DEX injections.
  • Protein levels of insulin signaling components (IRS-1, IRS-2, AKT, mTOR), GR, and AR were measured in prostate tissue.
  • Epithelial proliferation was assessed by quantifying proliferating cell nuclear antigen (PCNA)-positive cells and AR-positive cells.

Main Results:

  • DEX treatment significantly decreased body weight but not prostate weight.
  • Prostate levels of IRS-1, IRS-2, AKT, mTOR, GR, and AR proteins were significantly reduced in DEX-treated rats.
  • AR-positive cell frequency and nuclear intensity decreased, and PCNA-positive cells were reduced 30-fold in DEX-treated rats.

Conclusions:

  • Reduced expression of IRS-1/IRS-2/AKT/mTOR in the prostate of DEX-treated rats is linked to observed morphological alterations.
  • Dexamethasone-induced insulin resistance impacts prostate cell signaling and proliferation, involving GR and AR pathways.

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