Targeted Elimination of Senescent Beta Cells Prevents Type 1 Diabetes.

Cell Metab 2019 May 21;29(5):1045-1060.e10. Epub 2019 Feb 21.

Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address:

Type 1 diabetes (T1D) is an organ-specific autoimmune disease characterized by hyperglycemia due to progressive loss of pancreatic beta cells. Immune-mediated beta cell destruction drives the disease, but whether beta cells actively participate in the pathogenesis remains unclear. Here, we show that during the natural history of T1D in humans and the non-obese diabetic (NOD) mouse model, a subset of beta cells acquires a senescence-associated secretory phenotype (SASP). Senescent beta cells upregulated pro-survival mediator Bcl-2, and treatment of NOD mice with Bcl-2 inhibitors selectively eliminated these cells without altering the abundance of the immune cell types involved in the disease. Significantly, elimination of senescent beta cells halted immune-mediated beta cell destruction and was sufficient to prevent diabetes. Our findings demonstrate that beta cell senescence is a significant component of the pathogenesis of T1D and indicate that clearance of senescent beta cells could be a new therapeutic approach for T1D.

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http://dx.doi.org/10.1016/j.cmet.2019.01.021DOI Listing
May 2019
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