Palmitate-induced beta-cell dysfunction is associated with excessive NO production and is reversed by thiazolidinedione-mediated inhibition of GPR40 transduction mechanisms.
Meidute Abaraviciene, Sandra ; Lundquist, Ingmar LU ; Galvanovskis, Juris LU ; Flodgren, Erik LU ; Olde, Björn LU and Salehi, S Albert LU
(2008)
In PLoS ONE
3(5).
- Abstract
- BACKGROUND: Type 2 diabetes often displays hyperlipidemia. We examined palmitate effects on pancreatic islet function in relation to FFA receptor GPR40, NO generation, insulin release, and the PPARgamma agonistic thiazolidinedione, rosiglitazone. PRINCIPAL FINDINGS: Rosiglitazone suppressed acute palmitate-stimulated GPR40-transduced PI hydrolysis in HEK293 cells and insulin release from MIN6c cells and mouse islets. Culturing islets 24 h with palmitate at 5 mmol/l glucose induced beta-cell iNOS expression as revealed by confocal microscopy and increased the activities of ncNOS and iNOS associated with suppression of glucose-stimulated insulin response. Rosiglitazone reversed these effects. The expression of iNOS after high-glucose... (More)
- BACKGROUND: Type 2 diabetes often displays hyperlipidemia. We examined palmitate effects on pancreatic islet function in relation to FFA receptor GPR40, NO generation, insulin release, and the PPARgamma agonistic thiazolidinedione, rosiglitazone. PRINCIPAL FINDINGS: Rosiglitazone suppressed acute palmitate-stimulated GPR40-transduced PI hydrolysis in HEK293 cells and insulin release from MIN6c cells and mouse islets. Culturing islets 24 h with palmitate at 5 mmol/l glucose induced beta-cell iNOS expression as revealed by confocal microscopy and increased the activities of ncNOS and iNOS associated with suppression of glucose-stimulated insulin response. Rosiglitazone reversed these effects. The expression of iNOS after high-glucose culturing was unaffected by rosiglitazone. Downregulation of GPR40 by antisense treatment abrogated GPR40 expression and suppressed palmitate-induced iNOS activity and insulin release. CONCLUSION: We conclude that, in addition to mediating acute FFA-stimulated insulin release, GPR40 is an important regulator of iNOS expression and dysfunctional insulin release during long-term exposure to FFA. The adverse effects of palmitate were counteracted by rosiglitazone at GPR40, suggesting that thiazolidinediones are beneficial for beta-cell function in hyperlipidemic type 2 diabetes. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1154197
- author
- Meidute Abaraviciene, Sandra
; Lundquist, Ingmar
LU
; Galvanovskis, Juris
LU
; Flodgren, Erik
LU
; Olde, Björn
LU
and Salehi, S Albert
LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 3
- issue
- 5
- article number
- e2182
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000262172800047
- pmid:18478115
- scopus:48249125013
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0002182
- language
- English
- LU publication?
- yes
- id
- bbe41b5c-df74-4e77-a76c-2ee794aa28e2 (old id 1154197)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/18478115?dopt=Abstract
- date added to LUP
- 2016-04-04 09:40:12
- date last changed
- 2024-02-11 14:15:17
@article{bbe41b5c-df74-4e77-a76c-2ee794aa28e2,
abstract = {{BACKGROUND: Type 2 diabetes often displays hyperlipidemia. We examined palmitate effects on pancreatic islet function in relation to FFA receptor GPR40, NO generation, insulin release, and the PPARgamma agonistic thiazolidinedione, rosiglitazone. PRINCIPAL FINDINGS: Rosiglitazone suppressed acute palmitate-stimulated GPR40-transduced PI hydrolysis in HEK293 cells and insulin release from MIN6c cells and mouse islets. Culturing islets 24 h with palmitate at 5 mmol/l glucose induced beta-cell iNOS expression as revealed by confocal microscopy and increased the activities of ncNOS and iNOS associated with suppression of glucose-stimulated insulin response. Rosiglitazone reversed these effects. The expression of iNOS after high-glucose culturing was unaffected by rosiglitazone. Downregulation of GPR40 by antisense treatment abrogated GPR40 expression and suppressed palmitate-induced iNOS activity and insulin release. CONCLUSION: We conclude that, in addition to mediating acute FFA-stimulated insulin release, GPR40 is an important regulator of iNOS expression and dysfunctional insulin release during long-term exposure to FFA. The adverse effects of palmitate were counteracted by rosiglitazone at GPR40, suggesting that thiazolidinediones are beneficial for beta-cell function in hyperlipidemic type 2 diabetes.}},
author = {{Meidute Abaraviciene, Sandra and Lundquist, Ingmar and Galvanovskis, Juris and Flodgren, Erik and Olde, Björn and Salehi, S Albert}},
issn = {{1932-6203}},
language = {{eng}},
number = {{5}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{Palmitate-induced beta-cell dysfunction is associated with excessive NO production and is reversed by thiazolidinedione-mediated inhibition of GPR40 transduction mechanisms.}},
url = {{http://dx.doi.org/10.1371/journal.pone.0002182}},
doi = {{10.1371/journal.pone.0002182}},
volume = {{3}},
year = {{2008}},
}