Exp Mol Med.  2009 Nov;41(11):782-792. 10.3858/emm.2009.41.11.084.

Effect of nicotinamide on early graft failure following intraportal islet transplantation

• Jung DY
• Park JB
• Joo SY
• Joh JW
• Kwon CH
• Kwon GY
• Kim SJ

• KMID: 1122279
• DOI: http://doi.org/10.3858/emm.2009.41.11.084

Abstract

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.

Keyword

diabetes mellitus, type 1; hepatectomy; islets of Langerhans; islets of Langerhans transplantation; niacinamide

MeSH Terms

Animals
Blood Glucose/metabolism
Chemokine CCL2/blood
Diabetes Mellitus, Experimental/blood/*therapy
Diabetes Mellitus, Type 1/blood/*therapy
Glucose Tolerance Test
Graft Rejection
Graft Survival/drug effects
Insulin-Secreting Cells/metabolism
*Islets of Langerhans Transplantation
Mice
Niacinamide/adverse effects/*pharmacology
Time Factors
Transplantation, Homologous
Vitamin B Complex/adverse effects/*pharmacology