title: Inhibition of GPR40 protects MIN6 β cells from palmitate-induced ER stress and apoptosis.
abstract: Chronic exposure to elevated concentration of free fatty acids (FFA) has been verified to induce endoplasmic reticulum (ER) stress, which leads to pancreatic β-cell apoptosis. As one of the medium and long chain FFA receptors, GPR40 is highly expressed in pancreatic β cells, mediates both acute and chronic effects of FFA on β-cell function, but the role of GPR40 in FFA-induced β-cell apoptosis remains unclear. In this study, we investigated the possible effects of GPR40 in palmitate-induced MIN6 β-cell apoptosis, and found that DC260126, a novel small molecular antagonist of GPR40, could protect MIN6 β cells from palmitate-induced ER stress and apoptosis. Similar results were observed in GPR40-deficient MIN6 cells, indicating that palmitate-induced β-cell apoptosis is at least partially dependent on ER stress pathway via GRP40.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Jinwei
authors.initials: J
authors.lastname: Wu
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
authors.forename: Weiliang
authors.initials: W
authors.lastname: Zhu
authors.forename: Heyao
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D017931:DNA Primers; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D019308:Palmitic Acid / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: C575478:DC26012; D017931:DNA Primers; C473036:Ffar1 protein, mouse; D043562:Receptors, G-Protein-Coupled; D013449:Sulfonamides; D019308:Palmitic Acid