Identification of small molecules that protect pancreatic β cells against endoplasmic reticulum stress-induced cell death.

ABSTRACT: Endoplasmic reticulum (ER) stress plays an important role in the decline in pancreatic β cell function and mass observed in type 2 diabetes. Here, we developed a novel β cell-based high-throughput screening assay to identify small molecules that protect β cells against ER stress-induced cell death. Mouse βTC6 cells were treated with the ER stressor tunicamycin to induce ER stress, and cell death was measured as a reduction in cellular ATP. A collection of 17600 compounds was screened for molecules that promote β cell survival. Of the approximately 80 positive hits, two selected compounds were able to increase the survival of human primary β cells and rodent β cell lines subjected to ER stressors including palmitate, a free fatty acid of pathological relevance to diabetes. These compounds a

SUBMITTER: Tran K 

PROVIDER: S-EPMC4273981 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature