DNA methylation of the glucagon-like peptide 1 receptor (GLP1R) in human pancreatic islets

Hall, Elin, Dayeh, Tasnim, Kirkpatrick, Clare L., Wollheim, Claes B., Nitert, Marloes Dekker and Ling, Charlotte (2013) DNA methylation of the glucagon-like peptide 1 receptor (GLP1R) in human pancreatic islets. BMC Medical Genetics, 14 76: 1-7. doi:10.1186/1471-2350-14-76


Author Hall, Elin
Dayeh, Tasnim
Kirkpatrick, Clare L.
Wollheim, Claes B.
Nitert, Marloes Dekker
Ling, Charlotte
Title DNA methylation of the glucagon-like peptide 1 receptor (GLP1R) in human pancreatic islets
Formatted title
DNA methylation of the glucagon-like peptide 1 receptor (GLP1R) in human pancreatic islets
Journal name BMC Medical Genetics   Check publisher's open access policy
ISSN 1471-2350
Publication date 2013-07-23
Sub-type Article (original research)
DOI 10.1186/1471-2350-14-76
Open Access Status DOI
Volume 14
Issue 76
Start page 1
End page 7
Total pages 7
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted abstract
Background Insulin secretion is enhanced upon the binding of Glucagon-like peptide-1 (GLP-1) to its receptor (GLP1R) in pancreatic β cells. Although a reduced expression of GLP1R in pancreatic islets from type 2 diabetic patients and hyperglycaemic rats has been established, it is still unknown if this is caused by differential DNA methylation of GLP1R in pancreatic islets of type 2 diabetic patients.

Methods In this study, DNA methylation levels of 12 CpG sites close to the transcription start site of GLP1R were analysed in pancreatic islets from 55 non-diabetic and 10 type 2 diabetic human donors as well as in β and α cells isolated from human pancreatic islets. DNA methylation of GLP1R was related to GLP1R expression, HbA1c levels and BMI. Moreover, mRNA expression of MECP2, DNMT1, DNMT3A and DNMT3B was analysed in pancreatic islets of the non-diabetic and type 2 diabetic donors.

Results One CpG unit, at position +199 and +205 bp from the transcription start site, showed a small increase in DNA methylation in islets from donors with type 2 diabetes compared to non-diabetic donors (0.53%, p=0.02). Furthermore, DNA methylation levels of one CpG site located 376 bp upstream of the transcription start site of GLP1R correlated negatively with GLP1R expression (rho=−0.34, p=0.008) but positively with BMI and HbA1c (rho=0.30, p=0.02 and rho=0.30, p=0.03, respectively). This specific CpG site is located in an area with known SP1 and SP3 transcription factor binding sites. Moreover, when we compared the DNA methylation of the GLP1R promoter in isolated human β and α cells, we found that it was higher in α- compared with β-cells (p=0.009). Finally, there was a trend towards decreased DNMT3A expression (p=0.056) in type 2 diabetic compared with non-diabetic islets.

Conclusions Together, our study shows that while BMI and HbA1c are positively associated with DNA methylation levels of GLP1R, its expression is negatively associated with DNA methylation of GLP1R in human pancreatic islets.
Keyword DNA methylation
Epigenetics
Glucagon-like peptide 1 receptor
GLP1R
Type 2 diabetes
Pancreatic islet
alpha Cells
beta Cells
DNMT1
DNMT3
Human skeletal-muscle
Gene-expression
Diabetes-mellitus
Down-regulation
GLP-1
Epigenetics
Rat
PPARGC1A
Promoter
SP3
α Cells
β Cells
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2014 Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 23 times in Thomson Reuters Web of Science Article | Citations
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