Amin Ardestani, Federico Paroni, Zahra Azizi, Supreet Kaur, Vrushali Khobragade, Ting Yuan, Thomas Frogne, Wufan Tao, Jose Oberholzer, Francois Pattou, Julie Kerr Conte, Kathrin Maedler
Apoptotic cell death is a hallmark of the loss of insulin-producing beta cells in all forms of diabetes mellitus. Current treatments fail to halt the decline in functional beta cell mass, and strategies to prevent beta cell apoptosis and dysfunction are urgently needed. Here, we identified mammalian sterile 20-like kinase-1 (MST1) as a critical regulator of apoptotic beta cell death and function. Under diabetogenic conditions, MST1 was strongly activated in beta cells in human and mouse islets and specifically induced the mitochondrial-dependent pathway of apoptosis through upregulation of the BCL-2 homology-3 (BH3)-only protein BIM...
April 2014: Nature Medicine