Improvement of Canine Islet Yield by Donor Pancreas Infusion With a p38MAPK Inhibitor

• DOI: 10.1097/tp.0b013e31817ef6c9
• Publication Date: 2009-03-05T20:46:21Z
• Authors: Taihei Ito; Keiko Omori; Jeffrey Rawson; Ivan Todorov; Sadaki Asari; Akio Kuroda; Jonathan Shintaku; Shin Itakura; Kevin Ferreri; Fouad Kandeel; Yoko Mullen
• Keywords: Beagle; Viaspan

Background. The activation of p38 mitogen-activated protein kinases (MAPK) is implicated in cold ischemia-reperfusion injury donor organs. islet isolation process, from pancreas procurement through collection, may activate p38MAPK leading to cytokine release and damage. This damage be prevented by treating pancreata with a inhibitor (p38IH) before preservation. Methods. Pancreata removed Beagle dogs were infused University Wisconsin solution containing the p38IH, SB203580, Pefabloc (n=6) or vehicle (dimethyl sulfoxide Pefabloc) alone (n=7), pancreatic duct preserved using two-layer method. After 20 22 hr, islets isolated 3000 IEQ/kg autotransplanted into corresponding dog monitor glucose metabolism. Results. p38IH-treated yielded significantly more than control (IEQ/g: 2134±297 vs. 1477±145 IEQ/g 65,012±9385 45,700±5103 IEQ/pancreas; P<0.05). Apoptotic β-cell percentages assessed laser scanning cytometry lower controls (44%±9.4% 61.6%±4.8%, Tumor necrosis factor-α expression real-time reverse transcription polymerase chain reaction was group controls. All (3000 IEQ/kg) transplanted (n=5) became euglycemic versus four five that received untreated islets. Plasma C-peptide levels after glucagon challenge higher animals receiving (n=4) (0.40±0.78 0.21±0.05 ng/mL, Conclusions. Infusion p38IH preservation suppresses release, prevents apoptosis, improves yield no adverse effect on function transplantation. treatment human improve for use clinical