Abstract:
OBJECTIVES:Previously, we showed that diazoxide (DZ), an effective ischemic preconditioning agent, protected rodent pancreas against ischemia-reperfusion injury. Here, we further investigate whether DZ supplementation to University of Wisconsin (UW) solution during pancreas procurement and islet isolation has similar cytoprotection in a preclinical nonhuman primate model. METHODS:Cynomolgus monkey pancreata were flushed with UW or UW + 150 μM DZ during procurement and preserved for 8 hours before islet isolation. RESULTS:First, a significantly higher islet yield was observed in UW + DZ than in UW (57,887 vs 23,574 IEq/pancreas and 5396 vs 1646 IEq/g). Second, the DZ treated islets had significantly lower apoptotic cells per islet (1.64% vs 9.85%). Third, DZ significantly inhibited ROS surge during reperfusion with a dose-response manner. Fourth, DZ improved in vitro function of isolated islets determined by mitochondrial potentials and calcium influx in responses to glucose and KCI. Fifth, the DZ treated islets had much higher cure rate and better glycemia control in diabetic mice transplant model. CONCLUSIONS:This study showed a strong mitochondrial protection of DZ on nonhuman primate islets against ischemia-reperfusion injury that provides strong evidence for its clinical application in islet and pancreas transplantation.
journal_name
Pancreasjournal_title
Pancreasauthors
Wang Y,Qi M,McGarrigle JJ,Xing Y,Mendoza-Elias JE,Bochenek M,Marchese E,He Y,Oberholzer Jdoi
10.1097/MPA.0000000000001557subject
Has Abstractpub_date
2020-05-01 00:00:00pages
706-713issue
5eissn
0885-3177issn
1536-4828pii
00006676-202005000-00016journal_volume
49pub_type
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