GPR40 is a G protein–coupled receptor highly expressed in β-cells and activated by long-chain fatty acids. Loss of function of GPR40 via small interfering RNA, antisense oligonucleotides, pharmacological inhibition, or gene deletion has shown that GPR40 mediates, at least in part, fatty acid potentiation of glucose-induced insulin secretion. Although the role of GPR40 in the acute effects of fatty acid is relatively well established, its potential contribution to chronic deleterious effects of fatty acids on β-cell function has remained controversial.
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