PMID- 20692455
OWN - NLM
STAT- MEDLINE
DCOM- 20110114
LR  - 20181217
IS  - 1873-2623 (Electronic)
IS  - 0041-1345 (Linking)
VI  - 42
IP  - 6
DP  - 2010 Jul-Aug
TI  - 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.
PG  - 2247-9
LID - 10.1016/j.transproceed.2010.05.039 [doi]
AB  - 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.
CI  - Copyright 2010 Elsevier Inc. All rights reserved.
FAU - Del Guerra, S
AU  - Del Guerra S
AD  - Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy.
FAU - D'Aleo, V
AU  - D'Aleo V
FAU - Gualtierotti, G
AU  - Gualtierotti G
FAU - Filipponi, F
AU  - Filipponi F
FAU - Boggi, U
AU  - Boggi U
FAU - De Simone, P
AU  - De Simone P
FAU - Vistoli, F
AU  - Vistoli F
FAU - Del Prato, S
AU  - Del Prato S
FAU - Marchetti, P
AU  - Marchetti P
FAU - Lupi, R
AU  - Lupi R
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Transplant Proc
JT  - Transplantation proceedings
JID - 0243532
RN  - 0 (Chemokine CCL2)
RN  - 0 (Insulin)
RN  - 0 (RNA, Messenger)
RN  - 5Z93L87A1R (Guanine)
RN  - IY9XDZ35W2 (Glucose)
RN  - JAC85A2161 (Adenine)
SB  - IM
MH  - Adenine/analysis
MH  - Chemokine CCL2/*genetics
MH  - Diabetes Mellitus, Type 1/surgery
MH  - Gene Expression Regulation
MH  - Glucose/pharmacology
MH  - Guanine/analysis
MH  - Humans
MH  - Inflammation/etiology/genetics
MH  - Insulin/metabolism
MH  - Insulin Secretion
MH  - Islets of Langerhans/drug effects/metabolism/*physiology
MH  - Islets of Langerhans Transplantation/adverse effects
MH  - Polymorphism, Genetic
MH  - *Polymorphism, Single Nucleotide
MH  - RNA, Messenger/genetics
MH  - Regulatory Sequences, Nucleic Acid/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tissue Donors
EDAT- 2010/08/10 06:00
MHDA- 2011/01/15 06:00
CRDT- 2010/08/10 06:00
PHST- 2010/08/10 06:00 [entrez]
PHST- 2010/08/10 06:00 [pubmed]
PHST- 2011/01/15 06:00 [medline]
AID - S0041-1345(10)00697-4 [pii]
AID - 10.1016/j.transproceed.2010.05.039 [doi]
PST - ppublish
SO  - Transplant Proc. 2010 Jul-Aug;42(6):2247-9. doi: 
      10.1016/j.transproceed.2010.05.039.