Bcl-2 proteins in diabetes: mitochondrial pathways of β-cell death and dysfunction

Trends Cell Biol. 2011 Jul;21(7):424-31. doi: 10.1016/j.tcb.2011.03.001. Epub 2011 Apr 12.


Diabetes is a metabolic disease affecting nearly 300 million individuals worldwide. Both types of diabetes (1 and 2) are characterized by loss of functional pancreatic β-cell mass causing different degrees of insulin deficiency. The Bcl-2 family has a double-edged effect in diabetes. These proteins are crucial controllers of the mitochondrial pathway of β-cell apoptosis induced by pro-inflammatory cytokines or lipotoxicity. In parallel, some Bcl-2 members also regulate glucose metabolism and β-cell function. In this review, we describe the role of Bcl-2 proteins in β-cell homeostasis and death. We focus on how these proteins interact, their contribution to the crosstalk between endoplasmic reticulum stress and mitochondrial permeabilization, their context-dependent usage following different pro-apoptotic stimuli, and their role in β-cell physiology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Death
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus / pathology*
  • Humans
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology*
  • Mitochondria / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*


  • Proto-Oncogene Proteins c-bcl-2