Cytokine-induced apoptotic cell death in a mouse pancreatic beta-cell line: inhibition by Bcl-2

Diabetologia. 1996 May;39(5):530-6. doi: 10.1007/BF00403299.


Cytokines are thought to contribute to the induction of pancreatic beta-cell destruction in insulin-dependent diabetes mellitus. The molecular mechanisms that underlie beta-cell death were investigated by studying cytokine-induced cell death in beta-cell lines. A combination of three cytokines (interleukin-1 beta, tumour necrosis factor-alpha, and interferon-gamma) induced apoptotic cell death in the mouse pancreatic beta-cell line beta TC1, as judged from the appearance of cells with hypodiploid nuclei and oligonucleosomal DNA fragmentation. The same treatment also induced apoptosis in the mouse pancreatic alpha-cell line alpha TC1 and the NOD/Lt mouse beta-cell line NIT-1, although to a lesser extent than in beta TC1 cells. The abundance of endogenous Bcl-2 in beta TC1 cells was lower than that in the other two cell lines. Overexpression of human Bcl-2 in beta TC1 cells partially protected them from cytokine-induced cell death. These results suggest that apoptosis may be responsible, at least in part, for cytokine-induced beta-cell destruction and that Bcl-2 prevents apoptosis in pancreatic islet cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Cytokines / pharmacology*
  • DNA, Neoplasm / analysis
  • Drug Interactions
  • GTP-Binding Proteins / biosynthesis
  • Gene Expression
  • Humans
  • Insulinoma
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • Islets of Langerhans
  • Mice
  • Pancreatic Neoplasms
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogenes*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / pharmacology
  • Transfection
  • Tumor Necrosis Factor-alpha / pharmacology


  • Cytokines
  • DNA, Neoplasm
  • Interleukin-1
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • GTP-Binding Proteins