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dc.contributor.authorAkiyama, Masaruen_US
dc.contributor.authorLiew, Chong Weeen_US
dc.contributor.authorLu, Shushengen_US
dc.contributor.authorHu, Jiangen_US
dc.contributor.authorMartinez, Rachaelen_US
dc.contributor.authorHambro, Benen_US
dc.contributor.authorKennedy, Robert T.en_US
dc.contributor.authorKulkarni, Rohit N.en_US
dc.date.accessioned2014-08-13T14:00:08Z
dc.date.issued2013en_US
dc.identifier.citationAkiyama, Masaru, Chong Wee Liew, Shusheng Lu, Jiang Hu, Rachael Martinez, Ben Hambro, Robert T. Kennedy, and Rohit N. Kulkarni. 2013. “X-Box Binding Protein 1 Is Essential for Insulin Regulation of Pancreatic α-Cell Function.” Diabetes 62 (7): 2439-2449. doi:10.2337/db12-1747. http://dx.doi.org/10.2337/db12-1747.en
dc.identifier.issn0012-1797en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12717570
dc.description.abstractPatients with type 2 diabetes (T2D) often exhibit hyperglucagonemia despite hyperglycemia, implicating defective α-cell function. Although endoplasmic reticulum (ER) stress has been suggested to underlie β-cell dysfunction in T2D, its role in α-cell biology remains unclear. X-box binding protein 1 (XBP1) is a transcription factor that plays a crucial role in the unfolded protein response (UPR), and its deficiency in β-cells has been reported to impair insulin secretion, leading to glucose intolerance. To evaluate the role of XBP1 in α-cells, we created complementary in vivo (α-cell–specific XBP1 knockout [αXBPKO] mice) and in vitro (stable XBP1 knockdown α-cell line [αXBPKD]) models. The αXBPKO mice exhibited glucose intolerance, mild insulin resistance, and an inability to suppress glucagon secretion after glucose stimulation. αXBPKD cells exhibited activation of inositol-requiring enzyme 1, an upstream activator of XBP1, leading to phosphorylation of Jun NH2-terminal kinase. Interestingly, insulin treatment of αXBPKD cells reduced tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) (pY896) and phosphorylation of Akt while enhancing serine phosphorylation (pS307) of IRS1. Consequently, the αXBPKD cells exhibited blunted suppression of glucagon secretion after insulin treatment in the presence of high glucose. Together, these data indicate that XBP1 deficiency in pancreatic α-cells induces altered insulin signaling and dysfunctional glucagon secretion.en
dc.language.isoen_USen
dc.publisherAmerican Diabetes Associationen
dc.relation.isversionofdoi:10.2337/db12-1747en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712068/pdf/en
dash.licenseLAAen_US
dc.subjectIslet Studiesen
dc.titleX-Box Binding Protein 1 Is Essential for Insulin Regulation of Pancreatic α-Cell Functionen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalDiabetesen
dash.depositing.authorKulkarni, Rohit N.en_US
dc.date.available2014-08-13T14:00:08Z
dc.identifier.doi10.2337/db12-1747*
dash.contributor.affiliatedKulkarni, Rohit


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