Donor pretreatment with DHMEQ improves islet transplantation

The Journal of Surgical Research
Tohru TakahashiSatoru Todo

Abstract

Currently, pancreatic islet transplantation to achieve normoglycemia in insulin-dependent diabetes mellitus (IDDM) requires two or more donors. This may be due to the inability to transplant functionally preserved and viable islets after isolation. Islets have already been subjected to various harmful stresses during the isolation process leading to apoptosis. One of the intracellular signaling pathways, the transcription factor nuclear factor-kappaB (NF-kappaB)-related pathway, is relevant to the mechanism of beta-cell apoptosis in isolated islets. We attempted to prevent islet apoptosis during isolation by a novel NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ). DHMEQ was injected intraperitoneally into donor mice 2 h prior to isolation. NF-kappaB activation, the functioning of isolated islets, apoptosis after isolation, and cytokine- and apoptosis-related genes were analyzed. After 160 equivalents of islets were transplanted into diabetic mice, graft survival and function were evaluated. Intra-islet NF-kappaB was activated immediately after isolation, and DHMEQ inhibited NF-kappaB activation without deterioration of islet function. DHMEQ significantly prevented apoptosis by inhibiting caspase 3/7 activities and d...Continue Reading

References

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Apr 15, 2000·Pancreas·S ParaskevasL Rosenberg
Jun 15, 2000·Bioorganic & Medicinal Chemistry Letters·N MatsumotoK Umezawa
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Apr 18, 2007·Cell Transplantation·Juliet A Emamaullee, A M James Shapiro

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Citations

Mar 19, 2013·Internal and Emergency Medicine·Kulrawee SidthipongKazuo Umezawa
Aug 6, 2013·Current Diabetes Reports·Antonio CitroLorenzo Piemonti
Aug 17, 2014·Advances in Biological Regulation·Tamami Ukaji, Kazuo Umezawa
Mar 10, 2016·Upsala Journal of Medical Sciences·Aileen J F KingNils Welsh
Mar 25, 2016·World Journal of Transplantation·Uriel BarkaiPaul de Vos
Nov 10, 2017·Current Opinion in Organ Transplantation·Nathan W Zammit, Shane T Grey

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