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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Tissue-specific methylation of human insulin gene and PCR assay for monitoring beta cell death
PLoS ONE, Volume 9, No. 4, Article e94591, Year 2014
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Description
The onset of metabolic dysregulation in type 1 diabetes (T1D) occurs after autoimmune destruction of the majority of pancreatic insulin-producing beta cells. We previously demonstrated that the DNA encoding the insulin gene is uniquely unmethylated in these cells and then developed a methylation-specific PCR (MSP) assay to identify circulating beta cell DNA in streptozotocin-treated mice prior to the rise in blood glucose. The current study extends to autoimmune non-obese diabetic (NOD) mice and humans, showing in NOD mice that beta cell death occurs six weeks before the rise in blood sugar and coincides with the onset of islet infiltration by immune cells, demonstrating the utility of MSP for monitoring T1D. We previously reported unique patterns of methylation of the human insulin gene, and now extend this to other human tissues. The methylation patterns of the human insulin promoter, intron 1, exon 2, and intron 2 were determined in several normal human tissues. Similar to our previous report, the human insulin promoter was unmethylated in beta cells, but methylated in all other tissues tested. In contrast, intron 1, exon 2 and intron 2 did not exhibit any tissue-specific DNA methylation pattern. Subsequently, a human MSP assay was developed based on the methylation pattern of the insulin promoter and human islet DNA was successfully detected in circulation of T1D patients after islet transplantation therapy. Signal levels of normal controls and pre-transplant samples were shown to be similar, but increased dramatically after islet transplantation. In plasma the signal declines with time but in whole blood remains elevated for at least two weeks, indicating that association of beta cell DNA with blood cells prolongs the signal. This assay provides an effective method to monitor beta cell destruction in early T1D and in islet transplantation therapy. © 2014 Husseiny et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3983232/bin/pone.0094591.s001.tiff
https://efashare.b-cdn.net/share/pmc/articles/PMC3983232/bin/pone.0094591.s002.tiff
https://efashare.b-cdn.net/share/pmc/articles/PMC3983232/bin/pone.0094591.s003.tiff
https://efashare.b-cdn.net/share/pmc/articles/PMC3983232/bin/pone.0094591.s004.tiff
https://efashare.b-cdn.net/share/pmc/articles/PMC3983232/bin/pone.0094591.s005.docx
https://efashare.b-cdn.net/share/pmc/articles/PMC3983232/bin/pone.0094591.s006.docx
Authors & Co-Authors
Husseiny, Mohamed Ibrahim
United States, Duarte
City of Hope National Med Center
Egypt, Zagazig
Faculty of Pharmacy
Kaye, Alexander
United States, Duarte
City of Hope National Med Center
Zebadua, Emily
United States, Duarte
City of Hope National Med Center
Kandeel, Fouad R.
United States, Duarte
City of Hope National Med Center
Ferreri, Kevin
United States, Duarte
City of Hope National Med Center
Statistics
Citations: 61
Authors: 5
Affiliations: 2
Identifiers
Doi:
10.1371/journal.pone.0094591
e-ISSN:
19326203
Research Areas
Genetics And Genomics
Noncommunicable Diseases