Effect of nicotinamide on early graft failure following intraportal islet transplantation.
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.
Jung
Da-Yeon
DY
Transplantation Research Center, Samsung Biomedical Research Institute, Seoul, Korea.
Park
Jae Berm
JB
Joo
Sung-Yeon
SY
Joh
Jae-Won
JW
Kwon
Choon-Hyuck
CH
Kwon
Ghee-Young
GY
Kim
Sung-Joo
SJ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018932:Chemokine CCL2 / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000628:therapy*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000628:therapy*; D005951:Glucose Tolerance Test; D006084:Graft Rejection; D006085:Graft Survival / Q000187:drug effects; D050417:Insulin-Secreting Cells / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D051379:Mice; D009536:Niacinamide / Q000009:adverse effects / Q000494:pharmacology*; D013997:Time Factors; D014184:Transplantation, Homologous; D014803:Vitamin B Complex / Q000009:adverse effects / Q000494:pharmacology*
D001786:Blood Glucose; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D014803:Vitamin B Complex; D009536:Niacinamide