A live-cell, high-content imaging survey of 206 endogenous factors across five stress conditions reveals context-dependent survival effects in mouse primary beta cells
Abstract
Beta cell death is a hallmark of diabetes. It is not known whether specific cellular stresses associated with type 1 or type 2 diabetes 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. Primary mouse islet cells were cultured in conditions mimicking five type 1 or type 2 diabetes-related stresses: basal 5 mmol/l glucose, cytokine cocktail (25 ng/ml TNF-α, 10 ng/ml IL-1β, 10 ng/ml IFN-γ), 1 μmol/l thapsigargin, 1.5 mmol/l palmitate and 20 mmol/l glucose (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. Our survey pointed to survival factors exhibiting generalised protective effects across conditions meant to model different types of diabetes and stages of the diseases. For example, our survey and follow-up experiments suggested that OLFM1 is a novel protective factor for mouse and human beta cells across multiple conditions. Most strikingly, we also found specific protective survival factors for each model stress condition. For exa...Continue Reading
References
Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin
Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells
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