A live-cell, high-content imaging survey of 206 endogenous factors across five stress conditions reveals context-dependent survival effects in XXXX primary beta cells.

@entity1 @entity71352 @entity71353 @entity2426 @entity66 @entity6 @entity19 @entity635 @entity637 @entity413
AIMS/HYPOTHESIS: Beta cell death is a hallmark of @entity6 . It is not known whether specific cellular stresses associated with type 1 or type 2 @entity6 require specific factors to protect pancreatic beta cells. No systematic comparison of endogenous soluble factors in the context of multiple pro-apoptotic conditions has been published. METHODS: Primary @entity19 islet cells were cultured in conditions mimicking five type 1 or type 2 @entity6 -related stresses: basal 5  mmol/l @entity413 , cytokine cocktail (25  ng/ml @entity637 , 10  ng/ml @entity635 , 10  ng/ml IFN-y), 1   mol/l @entity2426 , 1.5  mmol/l palmitate and 20  mmol/l @entity413 (all in the absence of serum). We surveyed the effects of a library of 206 endogenous factors (selected based on islet expression of their receptors) on islet cell survival through multi-parameter, live-cell imaging. RESULTS: Our survey pointed to survival factors exhibiting generalised protective effects across conditions meant to model different types of @entity6 and stages of the diseases. For example, our survey and follow-up experiments suggested that @entity71352 is a novel protective factor for @entity19 and @entity1 beta cells across multiple conditions. Most strikingly, we also found specific protective survival factors for each model @entity66 . For example, @entity71353 ( @entity71353 ) was toxic to islet cells in the serum-free baseline and serum-free 20  mmol/l @entity413 conditions, but protective in the context of lipotoxicity. Rank product testing supported the consistency of our observations. CONCLUSIONS/INTERPRETATION: Collectively, our survey reveals previously unidentified islet cell survival factors and suggest their potential utility in individualised medicine.
