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dc.contributor.authorKeane, D.
dc.contributor.authorTakahashi, H.
dc.contributor.authorDhayal, S.
dc.contributor.authorMorgan, N.
dc.contributor.authorCuri, R.
dc.contributor.authorNewsholme, Philip
dc.identifier.citationKeane, Deirdre C. and Takahashi, Hilton K. and Dhayal, Shalinee and Morgan, Noel G. and Curi, Rui and Newsholme, Philip. 2011. Arachidonic acid actions on functional integrity and attenuation of the negative effects of palmitic acid in a clonal pancreatic ß-cell line. Clinical Science. 120: pp. 195-206.

Chronic exposure of pancreatic β-cells to saturated non-esterified fatty acids can lead to inhibition of insulin secretion and apoptosis. Several previous studies have demonstrated that saturated fatty acids such as PA (palmitic acid) are detrimental to β-cell function compared with unsaturated fatty acids. In the present study, we describe the effect of the polyunsaturated AA (arachidonic acid) on the function of the clonal pancreatic β-cell line BRIN-BD11 and demonstrate AA-dependent attenuation of PA effects. When added to β-cell incubations at 100 μM, AA can stimulate cell proliferation and chronic (24 h) basal insulin secretion. Microarray analysis and/or real-time PCR indicated significant AA-dependent up-regulation of genes involved in proliferation and fatty acid metabolism [e.g. Angptl (angiopoietin-like protein 4), Ech1 (peroxisomal ∆3,5, ∆2,4-dienoyl-CoA isomerase), Cox-1 (cyclo-oxygenase-1) and Cox-2, P<0.05]. Experiments using specific COX and LOX (lipoxygenase) inhibitors demonstrated the importance of COX-1 activity for acute (20 min) stimulation of insulin secretion, suggesting that AA metabolites may be responsible for the insulinotropic effects.Moreover, concomitant incubation of AA with PA dose-dependently attenuated the detrimental effects of the saturated fatty acid, so reducing apoptosis and decreasing parameters of oxidative stress [ROS (reactive oxygen species) and NO levels] while improving the GSH/GSSG ratio. AA decreased the protein expression of iNOS (inducible NO synthase), the p65 subunit of NF-κB (nuclear factor κB) and the p47 subunit of NADPH oxidase in PA-treated cells. These findings indicate that AA has an important regulatory and protective β-cell action, which may be beneficial to function and survival in the ‘lipotoxic’ environment commonly associated with Type 2 diabetes mellitus.

dc.publisherPortland Press Ltd.
dc.subjectpancreatic β-cell
dc.subjectType 2 diabetes mellitus
dc.subjectreactive oxygen species
dc.subjectarachidonic acid
dc.subjectpalmitic acid
dc.titleArachidonic acid actions on functional integrity and attenuation of the negative effects of palmitic acid in a clonal pancreatic ß-cell line
dc.typeJournal Article
dcterms.source.titleClinical Science

© 2011 The Author(s). The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Non-Commercial Licence ( which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited.

curtin.departmentSchool of Biomedical Sciences
curtin.accessStatusOpen access

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