Introduction PPARGC1A 1 PPARGC1A 2 PPARGC1A PPARGC1A 3 5 PPARGC1A 6 7 Obesity, reduced physical activity and ageing are well known risk factors for type 2 diabetes. However, all individuals exposed to an affluent environment do not develop the disease. One likely reason is that genetic variation modifies individual susceptibility to the environment. However, the environment could also modify genetic risk factors by influencing expression of a gene by DNA methylation or histone modifications. Cytosine residues occurring in CG dinucleotides are targets for DNA methylation and gene expression is usually reduced when DNA methylation takes place at a promoter. Whether DNA methylation influences gene expression in target tissues for type 2 diabetes and thereby the pathogenesis of the disease remains to be demonstrated. PPARGC1A PPARGC1A PPARGC1A Methods Multi-organ donors 1 Table 1 Clinical characteristics of type 2 diabetic and non-diabetic donors   Non-diabetic donors Type 2 diabetic donors p n 48 (30/18) 12 (6/6)   a a   Age (years) 53.2 ± 2.4 66.7 ± 2.4 <0.05 a a 2 24.8 ± 0.6 27.1 ± 1.0 <0.05 a a b 53.3 27.3   b 46.7 72.3   Data are expressed as mean ± SEM a b PPARGC1A Human pancreatic islets and experimental plan 8 9 Insulin secretion study 8 9 Animals 10 11 12 Niddm1f Niddm1i 13 15 16 Analysis of PPARGC1A mRNA expression in pancreatic islets A 260 A 280 PPARGC1A 8 PPARGC1A Downregulation of PGC-1α in human islets using silencing RNA (siRNA) PPARGC1A PPARGC1A PPARGC1A 2+ 2+ 2 Genotyping PPARGC1A 5 17 DNA methylation PPARGC1A http://www.urogene.org/methprimer/index.html PPARGC1A 1 Fig. 1 PPARGC1A PPARGC1A a b PPARGC1A PPARGC1A c PPARGC1A d PPARGC1A e f PPARGC1A −1 −1 g PPARGC1A −1 −1 r p p  Statistical methods PPARGC1A t Z p p Results PPARGC1A p 1 PPARGC1A PPARGC1A n n p 1 PPARGC1A n n 1 PPARGC1A PPARGC1A r p PPARGC1A PPARGC1A 1 PPARGC1A p 1 PPARGC1A p PPARGC1A r p −1 −1 p PPARGC1A p 1 PPARGC1A r p 1 PPARGC1A p p p PPARGC1A PPARGC1A PPARGC1A n 2 PPARGC1A p p p PPARGC1A p Fig. 2 PPARGC1A a PPARGC1A n b n c d PPARGC1A n p  PPARGC1A ob ob 7 PPARGC1A PPARGC1A p 3 PPARGC1A p 3 PPARGC1A 3 Fig. 3 PPARGC1A a n n 10 11 PPARGC1A b PPARGC1A n 12 n n n 13 15 p  Discussion PPARGC1A PPARGC1A PPARGC1A PPARGC1A PPARGC1A 2 18 PPARGC1A ob ob 7 PPARGC1A PPARGC1A PPARGC1A PPARGC1A PPARGC1A 3 4 PPARGC1A 5 PPARGC1A PPARGC1A PPARGC1A PPARGC1A 19 PPARGC1A PPARGC1A PPARGC1A PPARGC1A PPARGC1A PPARGC1A PPARGC1A 5 PPARGC1A PPARGC1A PPARGC1A PPARGC1A