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dc.contributor.authorBellenger, Jérôme
dc.contributor.authorBellenger, Sandrine
dc.contributor.authorBataille, Amandine
dc.contributor.authorNicolaou, Anna
dc.contributor.authorRialland, Mickaël
dc.contributor.authorTessier, Christian
dc.contributor.authorNarce, Michel
dc.contributor.authorMassey, Karen A.
dc.contributor.authorKang, Jing Xuan
dc.date.accessioned2013-02-22T21:08:51Z
dc.date.issued2011
dc.identifier.citationBellenger, Jérôme, Sandrine Bellenger, Amandine Bataille, Karen A. Massey, Anna Nicolaou, Mickaël Rialland, Christian Tessier, Jing X. Kang, and Michel Narce. 2011. High pancreatic n-3 fatty acids prevent STZ-induced diabetes in fat-1 mice: Inflammatory pathway inhibition. Diabetes 60(4): 1090-1099.en_US
dc.identifier.issn0012-1797en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10336909
dc.description.abstractObejctive: Because of confounding factors, the effects of dietary n-3 polyunsaturated fatty acids (PUFA) on type 1 diabetes remain to be clarified. We therefore evaluated whether fat-1 transgenic mice, a well-controlled experimental model endogenously synthesizing n-3 PUFA, were protected against streptozotocin (STZ)-induced diabetes. We then aimed to elucidate the in vivo response at the pancreatic level. Research Design and Methods: \(\beta\)-Cell destruction was produced by multiple low-doses STZ (MLD-STZ). Blood glucose level, plasma insulin level, and plasma lipid analysis were then performed. Pancreatic mRNA expression of cytokines, the monocyte chemoattractant protein, and GLUT2 were evaluated as well as pancreas nuclear factor (NF)-\(\kappa\)B p65 and inhibitor of \(\kappa\)B (I\(\kappa\)B) protein expression. Insulin and cleaved caspase-3 immunostaining and lipidomic analysis were performed in the pancreas. Results: STZ-induced fat-1 mice did not develop hyperglycemia compared with wild-type mice, and \(\beta\)-cell destruction was prevented as evidenced by lack of histological pancreatic damage or reduced insulin level. The prevention of \(\beta\)-cell destruction was associated with no proinflammatory cytokine induction (tumor necrosis factor-\(\alpha\), interleukin-1\(\beta\), inducible nitric oxide synthase) in the pancreas, a decreased NF-\(\kappa\)B, and increased I\(\kappa\)B pancreatic protein expression. In the fat-1–treated mice, proinflammatory arachidonic-derived mediators as prostaglandin E\(_2\) and 12-hydroxyeicosatetraenoic acid were decreased and the anti-inflammatory lipoxin A\(_4\) was detected. Moreover, the 18-hydroxyeicosapentaenoic acid, precursor of the anti-inflammatory resolvin E1, was highly increased. Conclusions: Collectively, these findings indicate that fat-1 mice were protected against MLD-STZ–induced diabetes and pointed out for the first time in vivo the beneficial effects of n-3 PUFA at the pancreatic level, on each step of the development of the pathology—inflammation, \(\beta\)-cell damage—through cytokine response and lipid mediator production.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Diabetes Associationen_US
dc.relation.isversionofdoi:10.2337/db10-0901en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3064083/pdf/en_US
dash.licenseLAA
dc.titleHigh Pancreatic n-3 Fatty Acids Prevent STZ-Induced Diabetes in Fat-1 Mice: Inflammatory Pathway Inhibitionen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalDiabetesen_US
dash.depositing.authorKang, Jing Xuan
dc.date.available2013-02-22T21:08:51Z
dc.identifier.doi10.2337/db10-0901*
dash.authorsorderedfalse
dash.contributor.affiliatedKang, Jing


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