Free fatty acid receptor 1 (FFA(1)R/GPR40) and its involvement in fatty-acid-stimulated insulin secretion.
Salehi, S Albert LU
; Flodgren, Erik
LU
; Nilsson, N
; Jimenez, Javier
LU
; Miyazaki, J
; Owman, Christer
LU
and Olde, Björn
LU
(2005)
In Cell and Tissue Research
322(2).
p.207-215
- Abstract
- Free fatty acids (FFA) have generally been proposed to regulate pancreatic insulin release by an intracellular mechanism involving inhibition of CPT-1. The recently de-orphanized G-protein coupled receptor, FFA(1)R/GPR40, has been shown to be essential for fatty-acid-stimulated insulin release in MIN6 mouse insulinoma cells. The CPT-1 inhibitor, 2-bromo palmitate (2BrP), was investigated for its ability to interact with mouse FFA(1)R/GPR40. It was found to inhibit phosphatidyl inositol hydrolysis induced by linoleic acid (LA) (100 mu M in all experiments) in HEK293 cells transfected with FFA(1)R/GPR40 and in the MIN6 subclone, MIN6c4. 2BrP also inhibited LA-stimulated insulin release from mouse pancreatic islets. Mouse islets were... (More)
- Free fatty acids (FFA) have generally been proposed to regulate pancreatic insulin release by an intracellular mechanism involving inhibition of CPT-1. The recently de-orphanized G-protein coupled receptor, FFA(1)R/GPR40, has been shown to be essential for fatty-acid-stimulated insulin release in MIN6 mouse insulinoma cells. The CPT-1 inhibitor, 2-bromo palmitate (2BrP), was investigated for its ability to interact with mouse FFA(1)R/GPR40. It was found to inhibit phosphatidyl inositol hydrolysis induced by linoleic acid (LA) (100 mu M in all experiments) in HEK293 cells transfected with FFA(1)R/GPR40 and in the MIN6 subclone, MIN6c4. 2BrP also inhibited LA-stimulated insulin release from mouse pancreatic islets. Mouse islets were subjected to antisense intervention by treatment with a FFA(1)R/GPR40-specific morpholino oligonucleotide for 48 h. Antisense treatment of islets suppressed LA-stimulated insulin release by 50% and by almost 100% when islets were pretreated with LA for 30 min before applying the antisense. Antisense treatment had no effect on tolbutamide-stimulated insulin release. Confocal microscopy using an FFA(1)R/GPR40-specific antibody revealed receptor expression largely localized to the plasma membrane of insulin-producing cells. Pretreating the islets with LA for 30 min followed by antisense oligonucleotide treatment for 48 h reduced the FFA(1)R/GPR40 immunoreactivity to background levels. The results demonstrate that FFA(1)R/GPR40 is inhibited by the CPT-1 inhibitor, 2BrP, and confirm that FFA(1)R/GPR40 is indeed necessary, at least in part, for fatty-acid-stimulated insulin release. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/143123
- author
- Salehi, S Albert
LU
; Flodgren, Erik
LU
; Nilsson, N
; Jimenez, Javier
LU
; Miyazaki, J
; Owman, Christer
LU
and Olde, Björn
LU
- organization
- publishing date
- 2005
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- 2-bromo palmitate, insulin, mouse (NMRI), GPR40, free fatty acid, pancreatic islet
- in
- Cell and Tissue Research
- volume
- 322
- issue
- 2
- pages
- 207 - 215
- publisher
- Springer
- external identifiers
-
- wos:000233483600004
- pmid:16044321
- scopus:27944449329
- ISSN
- 1432-0878
- DOI
- 10.1007/s00441-005-0017-z
- language
- English
- LU publication?
- yes
- id
- 5ed11aae-9433-4d22-8bc5-c1ec88fa97b3 (old id 143123)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16044321&dopt=Abstract
- date added to LUP
- 2016-04-01 12:00:35
- date last changed
- 2022-04-13 04:43:11
@article{5ed11aae-9433-4d22-8bc5-c1ec88fa97b3,
abstract = {{Free fatty acids (FFA) have generally been proposed to regulate pancreatic insulin release by an intracellular mechanism involving inhibition of CPT-1. The recently de-orphanized G-protein coupled receptor, FFA(1)R/GPR40, has been shown to be essential for fatty-acid-stimulated insulin release in MIN6 mouse insulinoma cells. The CPT-1 inhibitor, 2-bromo palmitate (2BrP), was investigated for its ability to interact with mouse FFA(1)R/GPR40. It was found to inhibit phosphatidyl inositol hydrolysis induced by linoleic acid (LA) (100 mu M in all experiments) in HEK293 cells transfected with FFA(1)R/GPR40 and in the MIN6 subclone, MIN6c4. 2BrP also inhibited LA-stimulated insulin release from mouse pancreatic islets. Mouse islets were subjected to antisense intervention by treatment with a FFA(1)R/GPR40-specific morpholino oligonucleotide for 48 h. Antisense treatment of islets suppressed LA-stimulated insulin release by 50% and by almost 100% when islets were pretreated with LA for 30 min before applying the antisense. Antisense treatment had no effect on tolbutamide-stimulated insulin release. Confocal microscopy using an FFA(1)R/GPR40-specific antibody revealed receptor expression largely localized to the plasma membrane of insulin-producing cells. Pretreating the islets with LA for 30 min followed by antisense oligonucleotide treatment for 48 h reduced the FFA(1)R/GPR40 immunoreactivity to background levels. The results demonstrate that FFA(1)R/GPR40 is inhibited by the CPT-1 inhibitor, 2BrP, and confirm that FFA(1)R/GPR40 is indeed necessary, at least in part, for fatty-acid-stimulated insulin release.}},
author = {{Salehi, S Albert and Flodgren, Erik and Nilsson, N and Jimenez, Javier and Miyazaki, J and Owman, Christer and Olde, Björn}},
issn = {{1432-0878}},
keywords = {{2-bromo palmitate; insulin; mouse (NMRI); GPR40; free fatty acid; pancreatic islet}},
language = {{eng}},
number = {{2}},
pages = {{207--215}},
publisher = {{Springer}},
series = {{Cell and Tissue Research}},
title = {{Free fatty acid receptor 1 (FFA(1)R/GPR40) and its involvement in fatty-acid-stimulated insulin secretion.}},
url = {{https://lup.lub.lu.se/search/files/2741631/624935.pdf}},
doi = {{10.1007/s00441-005-0017-z}},
volume = {{322}},
year = {{2005}},
}