A chemical chaperone 4-PBA ameliorates palmitate-induced inhibition of glucose-stimulated insulin secretion (GSIS).
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.
Choi
Sung-E
SE
Institute for Medical Science, Ajou University School of Medicine, Wonchon-dong san 5, Youngtong-gu, Gyunggi-do, 442-749 Suwon, Republic of Korea.
Lee
Youn-Jung
YJ
Jang
Hyun-Ju
HJ
Lee
Kwan-Woo
KW
Kim
Young-Soo
YS
Jun
Hee-Sook
HS
Kang
Sang Sun
SS
Chun
Jaesun
J
Kang
Yup
Y
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
C121358:4-phenylbutylamine; D002082:Butylamines; D007328:Insulin; D018832:Molecular Chaperones; D019308:Palmitic Acid; D005947:Glucose