Palmitate-induced beta-cell dysfunction is associated with excessive NO production and is reversed by thiazolidinedione-mediated inhibition of GPR40 transduction mechanisms.

<h4>Background</h4>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.<h4>Principal findings</h4...

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Autores principales:	Sandra Meidute Abaraviciene, Ingmar Lundquist, Juris Galvanovskis, Erik Flodgren, Björn Olde, Albert Salehi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4aa6fdb3020c4c02b4edec44f860efe3
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spelling	oai:doaj.org-article:4aa6fdb3020c4c02b4edec44f860efe32021-11-25T06:12:27ZPalmitate-induced beta-cell dysfunction is associated with excessive NO production and is reversed by thiazolidinedione-mediated inhibition of GPR40 transduction mechanisms.1932-620310.1371/journal.pone.0002182https://doaj.org/article/4aa6fdb3020c4c02b4edec44f860efe32008-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18478115/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Principal findings</h4>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.<h4>Conclusion</h4>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.Sandra Meidute AbaravicieneIngmar LundquistJuris GalvanovskisErik FlodgrenBjörn OldeAlbert SalehiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 5, p e2182 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sandra Meidute Abaraviciene Ingmar Lundquist Juris Galvanovskis Erik Flodgren Björn Olde Albert Salehi Palmitate-induced beta-cell dysfunction is associated with excessive NO production and is reversed by thiazolidinedione-mediated inhibition of GPR40 transduction mechanisms.
description	<h4>Background</h4>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.<h4>Principal findings</h4>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.<h4>Conclusion</h4>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.
format	article
author	Sandra Meidute Abaraviciene Ingmar Lundquist Juris Galvanovskis Erik Flodgren Björn Olde Albert Salehi
author_facet	Sandra Meidute Abaraviciene Ingmar Lundquist Juris Galvanovskis Erik Flodgren Björn Olde Albert Salehi
author_sort	Sandra Meidute Abaraviciene
title	Palmitate-induced beta-cell dysfunction is associated with excessive NO production and is reversed by thiazolidinedione-mediated inhibition of GPR40 transduction mechanisms.
title_short	Palmitate-induced beta-cell dysfunction is associated with excessive NO production and is reversed by thiazolidinedione-mediated inhibition of GPR40 transduction mechanisms.
title_full	Palmitate-induced beta-cell dysfunction is associated with excessive NO production and is reversed by thiazolidinedione-mediated inhibition of GPR40 transduction mechanisms.
title_fullStr	Palmitate-induced beta-cell dysfunction is associated with excessive NO production and is reversed by thiazolidinedione-mediated inhibition of GPR40 transduction mechanisms.
title_full_unstemmed	Palmitate-induced beta-cell dysfunction is associated with excessive NO production and is reversed by thiazolidinedione-mediated inhibition of GPR40 transduction mechanisms.
title_sort	palmitate-induced beta-cell dysfunction is associated with excessive no production and is reversed by thiazolidinedione-mediated inhibition of gpr40 transduction mechanisms.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/4aa6fdb3020c4c02b4edec44f860efe3
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Palmitate-induced beta-cell dysfunction is associated with excessive NO production and is reversed by thiazolidinedione-mediated inhibition of GPR40 transduction mechanisms.

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