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.
OBJECTIVE
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.
Del Guerra
S
S
Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy.
D'Aleo
V
V
Gualtierotti
G
G
Filipponi
F
F
Boggi
U
U
De Simone
P
P
Vistoli
F
F
Del Prato
S
S
Marchetti
P
P
Lupi
R
R
D000225:Adenine / Q000032:analysis; D018932:Chemokine CCL2 / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology; D006147:Guanine / Q000032:analysis; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000235:genetics; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014019:Tissue Donors
D018932:Chemokine CCL2; D007328:Insulin; D012333:RNA, Messenger; D006147:Guanine; D005947:Glucose; D000225:Adenine