PMID- 19641379 OWN - NLM STAT- MEDLINE DCOM- 20100128 LR - 20211020 IS - 2092-6413 (Electronic) IS - 1226-3613 (Print) IS - 1226-3613 (Linking) VI - 41 IP - 11 DP - 2009 Nov 30 TI - Effect of nicotinamide on early graft failure following intraportal islet transplantation. PG - 782-92 LID - 10.3858/emm.2009.41.11.084 [doi] AB - Intraportal islet transplantation (IPIT) may potentially cure Type 1 diabetes mellitus; however, graft failure in the early post-transplantation period presents a major obstacle. In this study, we tested the ability of nicotinamide to prevent early islet destruction in a syngeneic mouse model. Mice (C57BL/6) with chemically-induced diabetes received intraportal transplants of syngeneic islet tissue in various doses. Islets were cultured for 24 h in medium with or without 10 mM nicotinamide supplementation. Following IPIT, islet function was confirmed by an intraperitoneal glucose tolerance test (IPGTT) and hepatectomy. The effects of nicotinamide were evaluated by blood glucose concentration, serum monocyte chemoattractant protein-1 (MCP-1) concentration, and immunohistology at 3 h and 24 h after IPIT. Among the various islet doses, an infusion of 300 syngeneic islets treated with nicotinamide exhibited the greatest differences in glucose tolerance between recipients of treated and untreated (i.e., control) islets. One day after 300 islet equivalent (IEQ) transplantation, islets treated with nicotinamide were better granulated than the untreated islets (P=0.01), and the recipients displayed a slight decrease in serum MCP-1 concentration, as compared to controls. After 15 days, recipients of nicotinamide-pretreated islets showed higher levels of graft function (as measured by IPGTT) than controls. The pretreatment also prolonged graft survival (>100 days) and function; these were confirmed by partial hepatectomy, which led to the recurrence of diabetes. Pretreatment of islet grafts with nicotinamide may prevent their deterioration on the early period following IPIT in a syngeneic mouse model. FAU - Jung, Da-Yeon AU - Jung DY AD - Transplantation Research Center, Samsung Biomedical Research Institute, Seoul, Korea. FAU - Park, Jae Berm AU - Park JB FAU - Joo, Sung-Yeon AU - Joo SY FAU - Joh, Jae-Won AU - Joh JW FAU - Kwon, Choon-Hyuck AU - Kwon CH FAU - Kwon, Ghee-Young AU - Kwon GY FAU - Kim, Sung-Joo AU - Kim SJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Exp Mol Med JT - Experimental & molecular medicine JID - 9607880 RN - 0 (Blood Glucose) RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 12001-76-2 (Vitamin B Complex) RN - 25X51I8RD4 (Niacinamide) SB - IM MH - Animals MH - Blood Glucose/metabolism MH - Chemokine CCL2/blood MH - Diabetes Mellitus, Experimental/blood/*therapy MH - Diabetes Mellitus, Type 1/blood/*therapy MH - Glucose Tolerance Test MH - Graft Rejection MH - Graft Survival/drug effects MH - Insulin-Secreting Cells/metabolism MH - *Islets of Langerhans Transplantation MH - Mice MH - Niacinamide/adverse effects/*pharmacology MH - Time Factors MH - Transplantation, Homologous MH - Vitamin B Complex/adverse effects/*pharmacology PMC - PMC2788732 EDAT- 2009/07/31 09:00 MHDA- 2010/01/29 06:00 PMCR- 2009/11/30 CRDT- 2009/07/31 09:00 PHST- 2009/07/31 09:00 [entrez] PHST- 2009/07/31 09:00 [pubmed] PHST- 2010/01/29 06:00 [medline] PHST- 2009/11/30 00:00 [pmc-release] AID - 10.3858/emm.2009.41.11.084 [doi] PST - ppublish SO - Exp Mol Med. 2009 Nov 30;41(11):782-92. doi: 10.3858/emm.2009.41.11.084.