Insulin promoter DNA methylation correlates negatively with insulin gene expression and positively with HbA(1c) levels in human pancreatic islets.
(2011) In Diabetologia Dec. p.360-367- Abstract
- AIMS/HYPOTHESIS: Although recent studies propose that epigenetic factors influence insulin expression, the regulation of the insulin gene in type 2 diabetic islets is still not fully understood. Here, we examined DNA methylation of the insulin gene promoter in pancreatic islets from patients with type 2 diabetes and non-diabetic human donors and related it to insulin expression, HbA(1c) levels, BMI and age. METHODS: DNA methylation was analysed in 25 CpG sites of the insulin promoter and insulin mRNA expression was analysed using quantitative RT-PCR in pancreatic islets from nine donors with type 2 diabetes and 48 non-diabetic donors. RESULTS: Insulin mRNA expression (p = 0.002), insulin content (p = 0.004) and glucose-stimulated insulin... (More)
- AIMS/HYPOTHESIS: Although recent studies propose that epigenetic factors influence insulin expression, the regulation of the insulin gene in type 2 diabetic islets is still not fully understood. Here, we examined DNA methylation of the insulin gene promoter in pancreatic islets from patients with type 2 diabetes and non-diabetic human donors and related it to insulin expression, HbA(1c) levels, BMI and age. METHODS: DNA methylation was analysed in 25 CpG sites of the insulin promoter and insulin mRNA expression was analysed using quantitative RT-PCR in pancreatic islets from nine donors with type 2 diabetes and 48 non-diabetic donors. RESULTS: Insulin mRNA expression (p = 0.002), insulin content (p = 0.004) and glucose-stimulated insulin secretion (p = 0.04) were reduced in pancreatic islets from patients with type 2 diabetes compared with non-diabetic donors. Moreover, four CpG sites located 234 bp, 180 and 102 bp upstream and 63 bp downstream of the transcription start site (CpG -234, -180, -102 and +63, respectively), showed increased DNA methylation in type 2 diabetic compared with non-diabetic islets (7.8%, p = 0.03; 7.1%, p = 0.02; 4.4%, p = 0.03 and 9.3%, p = 0.03, respectively). While insulin mRNA expression correlated negatively (p < 1 × 10(-6)), the level of HbA(1c) correlated positively (p ≤ 0.01) with the degree of DNA methylation for CpG -234, -180 and +63. Furthermore, DNA methylation for nine additional CpG sites correlated negatively with insulin mRNA expression (p ≤ 0.01). Also, exposure to hyperglycaemia for 72 h increased insulin promoter DNA methylation in clonal rat beta cells (p = 0.005). CONCLUSIONS/INTERPRETATIONS: This study demonstrates that DNA methylation of the insulin promoter is increased in patients with type 2 diabetes and correlates negatively with insulin gene expression in human pancreatic islets. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1731605
- author
- Yang, Beatrice LU ; Dayeh, Tasnim LU ; Kirkpatrick, C L ; Taneera, Jalal LU ; Kumar, Rajesh LU ; Groop, Leif LU ; Wollheim, Claes LU ; Dekker Nitert, Marloes LU and Ling, Charlotte LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Diabetologia
- volume
- Dec
- pages
- 360 - 367
- publisher
- Springer
- external identifiers
-
- wos:000286001800022
- pmid:21104225
- scopus:78951472134
- pmid:21104225
- ISSN
- 1432-0428
- DOI
- 10.1007/s00125-010-1967-6
- language
- English
- LU publication?
- yes
- id
- 46d7740c-53a8-46fd-ad50-0dfdf963f7c3 (old id 1731605)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21104225?dopt=Abstract
- date added to LUP
- 2016-04-04 07:40:29
- date last changed
- 2024-04-26 20:39:09
@article{46d7740c-53a8-46fd-ad50-0dfdf963f7c3, abstract = {{AIMS/HYPOTHESIS: Although recent studies propose that epigenetic factors influence insulin expression, the regulation of the insulin gene in type 2 diabetic islets is still not fully understood. Here, we examined DNA methylation of the insulin gene promoter in pancreatic islets from patients with type 2 diabetes and non-diabetic human donors and related it to insulin expression, HbA(1c) levels, BMI and age. METHODS: DNA methylation was analysed in 25 CpG sites of the insulin promoter and insulin mRNA expression was analysed using quantitative RT-PCR in pancreatic islets from nine donors with type 2 diabetes and 48 non-diabetic donors. RESULTS: Insulin mRNA expression (p = 0.002), insulin content (p = 0.004) and glucose-stimulated insulin secretion (p = 0.04) were reduced in pancreatic islets from patients with type 2 diabetes compared with non-diabetic donors. Moreover, four CpG sites located 234 bp, 180 and 102 bp upstream and 63 bp downstream of the transcription start site (CpG -234, -180, -102 and +63, respectively), showed increased DNA methylation in type 2 diabetic compared with non-diabetic islets (7.8%, p = 0.03; 7.1%, p = 0.02; 4.4%, p = 0.03 and 9.3%, p = 0.03, respectively). While insulin mRNA expression correlated negatively (p < 1 × 10(-6)), the level of HbA(1c) correlated positively (p ≤ 0.01) with the degree of DNA methylation for CpG -234, -180 and +63. Furthermore, DNA methylation for nine additional CpG sites correlated negatively with insulin mRNA expression (p ≤ 0.01). Also, exposure to hyperglycaemia for 72 h increased insulin promoter DNA methylation in clonal rat beta cells (p = 0.005). CONCLUSIONS/INTERPRETATIONS: This study demonstrates that DNA methylation of the insulin promoter is increased in patients with type 2 diabetes and correlates negatively with insulin gene expression in human pancreatic islets.}}, author = {{Yang, Beatrice and Dayeh, Tasnim and Kirkpatrick, C L and Taneera, Jalal and Kumar, Rajesh and Groop, Leif and Wollheim, Claes and Dekker Nitert, Marloes and Ling, Charlotte}}, issn = {{1432-0428}}, language = {{eng}}, pages = {{360--367}}, publisher = {{Springer}}, series = {{Diabetologia}}, title = {{Insulin promoter DNA methylation correlates negatively with insulin gene expression and positively with HbA(1c) levels in human pancreatic islets.}}, url = {{http://dx.doi.org/10.1007/s00125-010-1967-6}}, doi = {{10.1007/s00125-010-1967-6}}, volume = {{Dec}}, year = {{2011}}, }