Insulin promoter DNA methylation correlates negatively with insulin gene expression and positively with HbA1c levels in human pancreatic islets

• DOI: 10.1007/s00125-010-1967-6
• Publication Date: 2010-11-22T15:13:12Z
• Authors: B. T. Yang; T. A. Dayeh; C. L. Kirkpatrick; J. Taneera; R. Kumar; L. Groop; C. B. Wollheim; M. D. Nitert; C. Ling
• Keywords: Pancreatic Islets; CpG site

Although recent studies propose that epigenetic factors influence insulin expression, the regulation of gene in type 2 diabetic islets is still not fully understood. Here, we examined DNA methylation promoter pancreatic from patients with diabetes and non-diabetic human donors related it to HbA(1c) levels, BMI age.DNA was analysed 25 CpG sites mRNA expression using quantitative RT-PCR nine 48 donors.Insulin (p = 0.002), content 0.004) glucose-stimulated secretion 0.04) were reduced compared donors. Moreover, four located 234 bp, 180 102 bp upstream 63 downstream transcription start site (CpG -234, -180, -102 +63, respectively), showed increased (7.8%, p 0.03; 7.1%, 0.02; 4.4%, 0.03 9.3%, 0.03, respectively). While correlated negatively < 1 × 10(-6)), level positively ≤ 0.01) degree for -180 +63. Furthermore, additional 0.01). Also, exposure hyperglycaemia 72 h clonal rat beta cells 0.005).This study demonstrates correlates islets.