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Modulation of growth-related gene expression and growth inhibition by cyclic adenosine 3',5'-monophosphate-elevating

C Lavergne1, B Breant, G Rosselin

  • 1Unité INSERM 55, Hôpital Saint-Antoine, Paris, France.

Endocrinology
|November 1, 1992
PubMed

Insights

Elevating cyclic AMP (cAMP) levels with IBMX or forskolin inhibits beta TC1 cell proliferation and insulin release. These compounds modulate cell cycle gene expression, impacting growth and function.

Area of Science:

  • Cell Biology
  • Endocrinology
  • Molecular Biology

Background:

  • The cAMP pathway plays a crucial role in cellular regulation.
  • Understanding beta-cell function is vital for diabetes research.
  • Regulation of beta-cell proliferation and function is complex.

Purpose of the Study:

  • To investigate the role of the cAMP pathway in regulating beta TC1 cell growth.
  • To examine how increased cAMP affects the cell cycle of quiescent beta TC1 cells.
  • To determine the impact of cAMP on insulin release and gene expression in beta TC1 cells.

Main Methods:

  • Utilized phosphodiesterase inhibitor IBMX and adenylate cyclase activator forskolin to modulate cAMP levels.
  • Measured intracellular cAMP concentrations and insulin release.
  • Analyzed the expression of cell cycle-related genes (c-fos, c-jun) and SV40 T-antigen mRNA.

Main Results:

  • Both IBMX and forskolin inhibited serum-induced proliferation in a dose-dependent manner.
  • cAMP levels increased significantly with IBMX and forskolin treatment.
  • These agents induced insulin release and modulated c-fos and c-jun gene expression.
  • IBMX and forskolin inhibited serum-induced SV40 T-antigen mRNA accumulation.

Conclusions:

  • Elevated cAMP levels inhibit beta TC1 cell proliferation and induce insulin release, characteristic of differentiated beta-cells.
  • The cAMP pathway influences cell cycle regulation through modulation of specific gene expression.
  • These findings provide insights into the control of beta-cell growth and function via cAMP signaling.

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