Insulin induces C2C12 cell proliferation and apoptosis through regulation of cyclin D1 and BAD expression

J Cell Biochem. 2013 Dec;114(12):2708-17. doi: 10.1002/jcb.24619.

Abstract

Insulin is a secreted peptide hormone identified in human pancreas to promote glucose utilization. Insulin has been observed to induce cell proliferation and myogenesis in C2C12 cells. The precise mechanisms underlying the proliferation of C2C12 cells induced by insulin remain unclear. In this study, we observed for the first time that 10 nM insulin treatment promotes C2C12 cell proliferation. Additionally, 50 and 100 nM insulin treatment induces C2C12 cell apoptosis. By utilizing real-time PCR and Western blotting analysis, we found that the mRNA levels of cyclinD1 and BAD are induced upon 10 and 50 nM/100 nM insulin treatment, respectively. The similar results were observed in C2C12 cells expressing GATA-6 or PPARα. Our results identify for the first time the downstream targets of insulin, cyclin D1, and BAD, elucidate a new molecular mechanism of insulin in promoting cell proliferation and apoptosis.

Keywords: BAD; CELL APOPTOSIS; CELL GROWTH; CYCLIN D1; INSULIN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation*
  • Cyclin D1 / genetics*
  • Flow Cytometry
  • GATA6 Transcription Factor / genetics
  • GATA6 Transcription Factor / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Insulin / genetics*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • PPAR alpha / genetics
  • PPAR alpha / metabolism
  • Signal Transduction
  • bcl-Associated Death Protein / genetics*
  • bcl-Associated Death Protein / metabolism

Substances

  • BAD protein, human
  • GATA6 Transcription Factor
  • Insulin
  • PPAR alpha
  • bcl-Associated Death Protein
  • Cyclin D1