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dc.contributor.authorAllister, Emma M.en_US
dc.contributor.authorRobson-Doucette, Christine A.en_US
dc.contributor.authorPrentice, Kacey J.en_US
dc.contributor.authorHardy, Alexandre B.en_US
dc.contributor.authorSultan, Sobiaen_US
dc.contributor.authorGaisano, Herbert Y.en_US
dc.contributor.authorKong, Dongen_US
dc.contributor.authorGilon, Patricken_US
dc.contributor.authorHerrera, Pedro L.en_US
dc.contributor.authorLowell, Bradford B.en_US
dc.contributor.authorWheeler, Michael B.en_US
dc.date.accessioned2014-07-07T18:15:06Z
dc.date.issued2013en_US
dc.identifier.citationAllister, E. M., C. A. Robson-Doucette, K. J. Prentice, A. B. Hardy, S. Sultan, H. Y. Gaisano, D. Kong, et al. 2013. “UCP2 Regulates the Glucagon Response to Fasting and Starvation.” Diabetes 62 (5): 1623-1633. doi:10.2337/db12-0981. http://dx.doi.org/10.2337/db12-0981.en
dc.identifier.issn0012-1797en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12407032
dc.description.abstractGlucagon is important for maintaining euglycemia during fasting/starvation, and abnormal glucagon secretion is associated with type 1 and type 2 diabetes; however, the mechanisms of hypoglycemia-induced glucagon secretion are poorly understood. We previously demonstrated that global deletion of mitochondrial uncoupling protein 2 (UCP2−/−) in mice impaired glucagon secretion from isolated islets. Therefore, UCP2 may contribute to the regulation of hypoglycemia-induced glucagon secretion, which is supported by our current finding that UCP2 expression is increased in nutrient-deprived murine and human islets. Further to this, we created α-cell–specific UCP2 knockout (UCP2AKO) mice, which we used to demonstrate that blood glucose recovery in response to hypoglycemia is impaired owing to attenuated glucagon secretion. UCP2-deleted α-cells have higher levels of intracellular reactive oxygen species (ROS) due to enhanced mitochondrial coupling, which translated into defective stimulus/secretion coupling. The effects of UCP2 deletion were mimicked by the UCP2 inhibitor genipin on both murine and human islets and also by application of exogenous ROS, confirming that changes in oxidative status and electrical activity directly reduce glucagon secretion. Therefore, α-cell UCP2 deletion perturbs the fasting/hypoglycemic glucagon response and shows that UCP2 is necessary for normal α-cell glucose sensing and the maintenance of euglycemia.en
dc.language.isoen_USen
dc.publisherAmerican Diabetes Associationen
dc.relation.isversionofdoi:10.2337/db12-0981en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636632/pdf/en
dash.licenseLAAen_US
dc.subjectIslet Studiesen
dc.titleUCP2 Regulates the Glucagon Response to Fasting and Starvationen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalDiabetesen
dash.depositing.authorKong, Dongen_US
dc.date.available2014-07-07T18:15:06Z
dc.identifier.doi10.2337/db12-0981*
dash.authorsorderedfalse
dash.contributor.affiliatedKong, Dong
dash.contributor.affiliatedLowell, Bradford


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