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dc.contributor.authorWang, Y.
dc.contributor.authorWang, S.
dc.contributor.authorHarvat, T.
dc.contributor.authorKinzer, K.
dc.contributor.authorZhang, L.
dc.contributor.authorFeng, F.
dc.contributor.authorQi, M.
dc.contributor.authorOberholzer, J.
dc.date.accessioned2016-05-06T17:48:24Z
dc.date.available2016-05-06T17:48:24Z
dc.date.issued2015-01
dc.identifier.bibliographicCitationWang, Y., Wang, S., Harvat, T., Kinzer, K., Zhang, L., Feng, F., Qi, M. and Oberholzer, J. Diazoxide, a KATP channel opener, prevents ischemia–reperfusion injury in rodent pancreatic islets. Cell Transplant. 2015. 24(1): 25-36. DOI: 10.3727/096368913X673441.en_US
dc.identifier.issn0963-6897
dc.identifier.urihttp://hdl.handle.net/10027/20523
dc.descriptionThis is a copy of an article published in Cell Transplantation © 2015 Cognizant Communication Corporation Publications.en_US
dc.description.abstractDiazoxide (DZ) is a pharmacological opener of ATP-sensitive K + channels that has been used for mimicking ischemic preconditioning and shows protection against ischemic damage. Here we investigated whether diazoxide supplementation to University of Wisconsin (UW) solution has cellular protection during islet isolation and improves in vivo islet transplant outcomes in a rodent ischemia model. C57/B6 mice pancreata were flushed with UW or UW + DZ solution and cold preserved for 6 or 10 h prior to islet isolation. Islet yield, in vitro and in vivo function, mitochondrial morphology, and apoptosis were evaluated. Significantly higher islet yields were observed in the UW + DZ group than in the UW group (237.5 ± 25.6 vs. 108.7 ± 49.3, p < 0.01). The islets from the UW + DZ group displayed a significantly higher glucose-induced insulin secretion (0.97 ng/ml ± 0.15 vs. 0.758 ng/ml ± 0.21, p = 0.009) and insulin content (60.96 ng/islet ± 13.94 vs. 42.09 ng/islet ± 8.15, p = 0.002). The DZ-treated islets had well-preserved mitochondrial morphology with superior responses of mitochondrial potentials, and calcium influx responded to glucose. A higher number of living cells and less late apoptotic cells were observed in the UW + DZ group (p < 0.05). Additionally, the islets from the UW + DZ group had a significantly higher cure rate and improved glucose tolerance. This study is the first to report mitoprotective effects of DZ for pancreas preservation and islet isolation. In the future, it will be necessary to further understand the underlying mechanism for the mitoprotection and to test this promising approach for pancreas preservation and the islet isolation process in nonhuman primates and ultimately humans.en_US
dc.description.sponsorshipThis study was supported by a startup grant by the College of Medicine at the University of Illinois at Chicago (J.O.), The Chicago Diabetes Project, a research grant by the Gift of Hope Foundation in Illinois (J.O. and Y.W.), and NIH R01 DK091526 (J.O.). The authors declare no conflicts of interest.en_US
dc.publisherCognizant Communication Corporationen_US
dc.subjectCold ischemiaen_US
dc.subjectDiazoxide (DZ)en_US
dc.subjectIslet isolationen_US
dc.subjectIslet transplantationen_US
dc.subjectMitoprotectionen_US
dc.subjectPancreas preservationen_US
dc.titleDiazoxide, a KATP Channel Opener, Prevents Ischemia‐Reperfusion Injury in Rodent Pancreatic Islets.en_US
dc.typeArticleen_US


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