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dc.contributor.authorAnnes, J. P.
dc.contributor.authorRyu, J. H.
dc.contributor.authorLam, K.
dc.contributor.authorCarolan, Peter Joseph
dc.contributor.authorUtz, K.
dc.contributor.authorHollister-Lock, J.
dc.contributor.authorAnthony, Anthony
dc.contributor.authorRubin, Lee
dc.contributor.authorWeir, Gordon Campbell
dc.contributor.authorMelton, Douglas A.
dc.date.accessioned2014-10-21T17:38:07Z
dc.date.issued2012
dc.identifierQuick submit: 2014-02-27T22:00:18-05:00
dc.identifier.citationAnnes, J. P., J. H. Ryu, K. Lam, P. J. Carolan, K. Utz, J. Hollister-Lock, A. C. Arvanites, L. L. Rubin, G. Weir, and D. A. Melton. 2012. “Adenosine Kinase Inhibition Selectively Promotes Rodent and Porcine Islet β-Cell Replication.” Proceedings of the National Academy of Sciences 109 (10) (March 6): 3915–3920. doi:10.1073/pnas.1201149109.en_US
dc.identifier.issn1091-6490en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13065025
dc.description.abstractDiabetes is a pathological condition characterized by relative insulin deficiency, persistent hyperglycemia, and, consequently, diffuse micro- and macrovascular disease. One therapeutic strategy is to amplify insulin-secretion capacity by increasing the number of the insulin-producing β cells without triggering a generalized proliferative response. Here, we present the development of a small-molecule screening platform for the identification of molecules that increase β-cell replication. Using this platform, we identify a class of compounds [adenosine kinase inhibitors (ADK-Is)] that promote replication of primary β cells in three species (mouse, rat, and pig). Furthermore, the replication effect of ADK-Is is cell type-selective: treatment of islet cell cultures with ADK-Is increases replication of β cells but not that of α cells, PP cells, or fibroblasts. Short-term in vivo treatment with an ADK-I also increases β-cell replication but not exocrine cell or hepatocyte replication. Therefore, we propose ADK inhibition as a strategy for the treatment of diabetes.en_US
dc.description.sponsorshipStem Cell and Regenerative Biologyen_US
dc.language.isoen_USen_US
dc.publisherProceedings of the National Academy of Sciencesen_US
dc.relation.isversionofdoi:10.1073/pnas.1201149109en_US
dash.licenseLAA
dc.titleAdenosine kinase inhibition selectively promotes rodent and porcine islet β-cell replicationen_US
dc.typeJournal Articleen_US
dc.date.updated2014-02-28T03:02:00Z
dc.description.versionVersion of Recorden_US
dc.rights.holderDouglas Melton
dc.relation.journalProceedings of the National Academy of Sciencesen_US
dash.depositing.authorMelton, Douglas A.
dc.date.available2014-10-21T17:38:07Z
dc.identifier.doi10.1073/pnas.1201149109*
workflow.legacycommentsPer new OSC interpretation, can post pub. FAR 2013en_US
dash.authorsorderedfalse
dash.contributor.affiliatedCarolan, Peter
dash.contributor.affiliatedArvanites, Anthony C.
dash.contributor.affiliatedWeir, Gordon
dash.contributor.affiliatedMelton, Douglas
dash.contributor.affiliatedRubin, Lee


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