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• W2012073608 abstract "Background and purpose: Exposure of pancreatic β‐cells to long‐chain free fatty acids leads to differential responses according to the chain length and degree of unsaturation. In particular, long‐chain saturated molecules such as palmitate (C16:0) cause apoptosis, whereas equivalent mono‐unsaturated species (for example, palmitoleate (C16:1)) are not overtly toxic. Moreover, mono‐unsaturates exert a powerful cytoprotective response against a range of proapoptotic stimuli. However, the structural requirements that determine cytoprotection have not been determined and form the basis of the present study. Experimental approach: BRIN‐BD11 and INS‐1 β‐cells were exposed either to the saturated fatty acid palmitate, or to serum withdrawal, to mediate cytotoxicity. The protective effects of a wide range of mono‐unsaturated fatty acid derivatives were tested in cytotoxicity assays. Effector caspase activity was also measured and correlated with viability. Key results: The cytotoxic actions of palmitate were inhibited dose‐dependently by long‐chain mono‐unsaturated fatty acids with a defined potency order C18:1>C16:1≫C14:1. The configuration of the double bond was also important with cis forms being more potent than trans forms. Alkylated mono‐unsaturated fatty‐acid derivates were also cytoprotective, although their efficacy declined as the alkyl chain length increased. Cytoprotection was achieved rapidly on addition of mono‐unsaturates and correlated with a rapid and dramatic inhibition of caspase‐3/7 activity in palmitate‐treated cells. Conclusions and implications: The data reveal the structural requirements that dictate the cytoprotective actions of mono‐unsaturated fatty acids in pancreatic β‐cells. Metabolic activation is not required and the data point at the potential involvement of a fatty acid receptor in mediating cytoprotection. British Journal of Pharmacology (2008) 153 , 1718–1727; doi: 10.1038/bjp.2008.43 ; published online 25 February 2008" @default.
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• W2012073608 date "2008-04-01" @default.
• W2012073608 modified "2023-10-15" @default.
• W2012073608 title "Structural requirements for the cytoprotective actions of mono-unsaturated fatty acids in the pancreatic β-cell line, BRIN-BD11" @default.
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• W2012073608 doi "https://doi.org/10.1038/bjp.2008.43" @default.
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