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

التفاصيل البيبلوغرافية
العنوان: DNA methylation of the glucagon-like peptide 1 receptor (GLP1R) in human pancreatic islets
المؤلفون: Clare L. Kirkpatrick, Claes B. Wollheim, Charlotte Ling, Elin Hall, Tasnim Dayeh, Marloes Dekker Nitert
المصدر: BMC Medical Genetics; 14(Jul,23), no 76 (2013)
BMC Medical Genetics, Vol. 14 (2013) P. 76
BMC Medical Genetics
بيانات النشر: BioMed Central (BMC), 2013.
سنة النشر: 2013
مصطلحات موضوعية: Male, Methyl-CpG-Binding Protein 2, α cells, DNA Methyltransferase 3A, Body Mass Index, Glucagon-Like Peptide 1/metabolism, Glucagon-Like Peptide 1, Insulin-Secreting Cells, Insulin Secretion, Gene expression, Receptors, Glucagon, Insulin, Genetics(clinical), GLP1R, DNA (Cytosine-5-)-Methyltransferases, DNA (Cytosine-5-)-Methyltransferase/genetics, Genetics (clinical), Glucagon-Secreting Cells/metabolism, Islets of Langerhans/cytology/metabolism, ddc:616, DNA methylation, Type 2 diabetes, Middle Aged, β cells, medicine.anatomical_structure, CpG site, Diabetes Mellitus, Type 2/genetics, Epigenetics, Female, Transcription Initiation Site, Medical Genetics, Research Article, DNA (Cytosine-5-)-Methyltransferase 1, Hemoglobin A, Glycosylated/genetics, medicine.medical_specialty, endocrine system, Methyl-CpG-Binding Protein 2/genetics, Biology, Glucagon-Like Peptide-1 Receptor, Receptors, Glucagon/genetics/metabolism, MECP2, Pancreatic islet, Islets of Langerhans, Insulin-Secreting Cells/metabolism, Sp3 transcription factor, Glucagon-like peptide 1 receptor, Internal medicine, Genetics, medicine, Humans, Binding site, ddc:612, Aged, Glycated Hemoglobin, Insulin/secretion, Pancreatic islets, DNMT1, DNMT3, DNA Methylation, Endocrinology, Diabetes Mellitus, Type 2, Glucagon-Secreting Cells, CpG Islands
الوصف: 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.
وصف الملف: application/pdf
اللغة: English
تدمد: 1471-2350
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5746328d009c06113082eda4a4e27b28
https://lup.lub.lu.se/record/3955639
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....5746328d009c06113082eda4a4e27b28
قاعدة البيانات: OpenAIRE
الوصف
تدمد:14712350