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419 TESTOSTERONE INHIBITION OF INSULIN SIGNALING PATHWAY GENES AND ADIPOGENIC GENES OBSERVED IN 3T3-L1 MOUSE PREADIPOCYTE CELLS BY EXPRESSION PROFILE.
  1. R. Singh,
  2. W. E. Taylor,
  3. R. Jasuja,
  4. B. Salehian,
  5. M. Braga,
  6. N. F. Gonzalez-Cadavid
  1. Charles Drew University and RCMI Molecular Medicine and Stem Cell Core, Los Angeles, CA

Abstract

The effect of testosterone administration on insulin sensitivity in patients with diabetes is poorly understood. Epidemiological studies in men indicate that type 2 diabetes mellitus and coronary artery disease are correlated with lower free testosterone concentrations in serum, while testosterone treatment in men is associated with increased insulin sensitivity. The purpose of this study is to analyze the gene expression profile in a preadipocyte cell line 3T3-L1, during growth in normal and adipogenic medium (AM), and subsequently study the effect of testosterone on expression of various genes involved in the insulin signaling pathway. We analyzed the effect of testosterone (100 nM) treatment on the expression pattern of 112 genes involved in insulin signaling pathway by GEArray (MM-030) from SuperArray. We observed that over 30 genes of this pathway are highly induced over five-fold during adipogenesis. Testosterone treatment led to significant change in at least 19 genes in this pathway. MEK 1, a component of MAP kinase pathway, was up-regulated after 48 hours of testosterone treatment, whereas we found significant inhibition in the expression of other MAP kinase pathway genes, Kras2, B-raf, MNK, and protein kinase C lambda. Inhibition was also observed for the primary target genes for insulin signaling (leptin and C/EBP-Beta) as well as PI-3 kinase pathway genes, eg, Frap 1, PIK3r2 (p85b subunit), and PAI-1, UCP-1, and Vegfa. We performed quantitative analysis by real-time reverse-transcription-PCR and Western blot analysis of various genes/proteins regulated by testosterone in this pathaway in order to have better understanding of the role of testosterone during insulin resistance, observing around three-fold inhibition of expression for leptin, C/EBP-Beta, PPAR-gamma2, and C/EBP-alpha. The information obtained from this study may provide the rationale for targeting key components responsible for insulin resistance in patients with type 2 diabetes.

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