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A chemical chaperone 4-PBA ameliorates palmitate-induced inhibition of glucose-stimulated insulin secretion (GSIS).

Authors
Choi, SE; Lee, YJ; Jang, HJ; Lee, KW; Kim, YS; Jun, HS; Kang, SS; Chun, J; Kang, Y
Citation
Archives of biochemistry and biophysics, 475(2):109-114, 2008
Journal Title
Archives of biochemistry and biophysics
ISSN
0003-98611096-0384
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.
MeSH terms
AnimalsButylamines/pharmacology*Cell Survival/drug effectsCells, CulturedDose-Response Relationship, DrugEndoplasmic Reticulum/drug effectsEndoplasmic Reticulum/physiologyGlucose/pharmacologyInsulin/secretion*Insulin-Secreting Cells/drug effects*Insulinoma/pathologyMolecular Chaperones/pharmacology*Oxidative Stress/drug effectsPalmitic Acid/pharmacology*Rats
DOI
10.1016/j.abb.2008.04.015
PMID
18455496
Appears in Collections:
Journal Papers > Research Organization > Chronic Inflammatory Disease Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Endocrinology & Metabolism
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
최, 성이이, 관우강, 엽
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