Multiparameter screening reveals a role for Na+ channels in cytokine-induced β-cell death.

摘要: Pancreatic β-cell death plays a role in both type 1 and 2 diabetes, but clinical treatments that specifically target survival have not yet been developed. We recently developed live-cell imaging-based, high-throughput screening methods capable of identifying factors modulate pancreatic death, with the hope finding drugs can intervene this process. In present study, we used high-content screen Prestwick Chemical Library small molecules to identify block cell resulting from exposure cocktail cytotoxic cytokines (25 ng/mL TNF-α, 10 IL-1β, IFN-γ). Data analysis self-organizing maps revealed 19 had profiles similar no cytokine condition, indicating protection. Carbamazepine, an antiepileptic Na+ channel inhibitor, was particularly interesting because channels are generally considered targets for antiapoptotic therapy diabetes function these i...