Leptin decreases apoptosis and alters BCL-2 : Bax ratio in clonal rodent pancreatic beta-cells

Diabetes Metab Res Rev. 2007 Sep;23(6):497-502. doi: 10.1002/dmrr.726.


Aims/hypothesis: The adipocyte derived peptide hormone leptin is known to regulate apoptosis and cell viability in several cells and tissues, as well as having several pancreatic islet beta-cell specific effects such as inhibition of glucose-stimulated insulin secretion. This study investigated the effects of leptin upon apoptosis induced by serum depletion and on expression of the apoptotic regulators B-cell leukaemia 2 gene product (BCL-2) and BCL2-associated X protein (Bax) in the glucose-responsive BRIN-BD11 beta-cell line.

Methods: BRIN-BD11 cells were cultured in RPMI 1640 and subsequently serum depleted +/- leptin (10 and 50 ng/mL) for 24 h. Cell viability and apoptosis were measured using a modified MTS assay and TUNEL/YO-PRO-1 assays, respectively. BCL-2 and Bax expression were measured by real-time PCR and Western blotting.

Results: Leptin caused a reduction in serum-depleted apoptosis, although it failed to have any effect on the overall cell viability, causing a 68% shift from apoptosis to necrosis. Leptin significantly increased the level of BCL-2 mRNA expression (150% compared to serum depletion alone), without altering Bax mRNA expression. At the protein level, leptin increased BCL-2 and decreased Bax, altering the BCL-2 : Bax ratio.

Conclusions: We conclude that leptin reduces apoptosis in beta-cells at physiological concentrations, possibly via its ability to up-regulate BCL-2 and Bax expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cell Line
  • Culture Media, Serum-Free
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / physiology*
  • Leptin / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism*


  • Culture Media, Serum-Free
  • Leptin
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • bcl-2-Associated X Protein