title: A chemical chaperone 4-PBA ameliorates palmitate-induced inhibition of glucose-stimulated insulin secretion (GSIS).
abstract: Free fatty acids (FFAs) are believed to be a stimulus to elicit beta cell dysfunction. The present study was undertaken to determine whether endoplasmic reticulum (ER) stress was involved in palmitate-induced inhibition of glucose-stimulated insulin secretion (GSIS) and whether reduction of ER stress using a chemical chaperone restored the GSIS-inhibition. Treatment of INS-1 cells with 300 microM palmitate for 24h elicited ER stress, showing increased levels of phospho-eIF2alpha, Bip and spliced XBP, and also induced GSIS-inhibition without reduction of cell viability. Replenishment with 4-phenyl butyric acid (4-PBA) as a chemical chaperone reduced the palmitate-induced-ER stress and significantly reversed the palmitate-induced GSIS-inhibition. Furthermore, 4-PBA ameliorated palmitate-induced GSIS-inhibition in primary rat islet cells. These data suggested that ER stress was involved in FFA-induced GSIS-inhibition and that the FFA-induced beta cell dysfunction could be ameliorated by treatment with a chemical chaperone.
authors.affiliation: Institute for Medical Science, Ajou University School of Medicine, Wonchon-dong san 5, Youngtong-gu, Gyunggi-do, 442-749 Suwon, Republic of Korea.
authors.forename: Sung-E
authors.initials: SE
authors.lastname: Choi
authors.forename: Youn-Jung
authors.initials: YJ
authors.lastname: Lee
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Jang
authors.forename: Kwan-Woo
authors.initials: KW
authors.lastname: Lee
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Hee-Sook
authors.initials: HS
authors.lastname: Jun
authors.forename: Sang Sun
authors.initials: SS
authors.lastname: Kang
authors.forename: Jaesun
authors.initials: J
authors.lastname: Chun
authors.forename: Yup
authors.initials: Y
authors.lastname: Kang
mesh_terms: D000818:Animals; D002082:Butylamines / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D007340:Insulinoma / Q000473:pathology; D018832:Molecular Chaperones / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D019308:Palmitic Acid / Q000494:pharmacology*; D051381:Rats
chemical_list: C121358:4-phenylbutylamine; D002082:Butylamines; D007328:Insulin; D018832:Molecular Chaperones; D019308:Palmitic Acid; D005947:Glucose