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

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

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Laboratory of Experimental Medicine, Université Libre de Bruxelles, Route de Lennik, 808, 1070, Brussels, Belgium.


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.

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