BACKGROUND AND AIMS: Islet transplantation is an attractive approach to treat type 1 diabetic patients. However, suboptimal islet engraftment still represents an unsolved problem. It has been shown that human islets release monocyte chemoattractant protein-1 (MCP-1), one of the most powerful macrophage chemokines, which may impair the fate of the transplant. The aim of this study was to evaluate the presence and role of MCP-1 in isolated human islets, including genotyping for a common polymorphism. METHODS: Pancreatic islets were isolated by enzymatic digestion and gradient purification from 41 nondiabetic multiorgan donors. We measured MCP-1 mRNA expression by quantitative real- time reverse-transcriptase polymerization chain reaction, analyzed the MCP-1 single nucleotide polymorphism, -2518 G/A (SNP, rs 1024611) and evaluated glucose-stimulated insulin release (IR; microU/islet/min). RESULTS: MCP-1 mRNA expression was found in all studied batches of islets. Overall, IR was significantly higher at 16.7 mmol/L than 3.3 mmol/L glucose. We observed a significant negative correlation between MCP-1 mRNA expression and stimulation index (SI). We found that MCP-1 mRNA expression was significantly higher in CC and CT compared with TT genotype groups. Finally, SI was significant lower in the CC with respect to the TT genotype group. CONCLUSIONS: These data show that MCP-1 gene expression regulated by the -2518 G/A polymorphism, is correlated with glucose-stimulated insulin release. The study of MCP-1 expression and genotype on isolated islets before transplantation may be useful to understand the inflammatory response after infusion of human islets into patients with type 1 diabetes mellitus.
|Autori interni:||FILIPPONI, FRANCO|
DEL PRATO, STEFANO
|Autori:||DEL GUERRA S; D'ALEO V; GUALTIEROTTI G; FILIPPONI F; BOGGI U; DE SIMONE P; VISTOLI F; DEL PRATO S; MARCHETTI P; LUPI R|
|Titolo:||A Common Polymorphism in the Monocyte Chemoattractant Protein-1 (MCP-1) Gene Regulatory Region Influences MCP-1 Expression and Function of Isolated Human Pancreatic Islets|
|Anno del prodotto:||2010|
|Digital Object Identifier (DOI):||10.1016/j.transproceed.2010.05.039|
|Appare nelle tipologie:||1.1 Articolo in rivista|