Marloes Dekker Nitert, associate researcher
Type 2 diabetes is a polygenic disease characterized by hyperglycaemia due to impaired pancreatic beta-cell function and insulin resistance in peripheral target tissues such as skeletal muscle, adipose tissue and the liver. The disease develops as a conspiracy between the genetic background and the environment. Recent genome-wide association studies have identified more than 40 genetic variants associated with type 2 diabetes. Moreover, ageing, physical inactivity and obesity represent non-genetic risk factors for type 2 diabetes. However, the interaction between genes and environment may also involve epigenetic factors, such as DNA methylation and histone modifications, to promote type 2 diabetes. Indeed, recent studies from our group and others propose that epigenetic factors may play an important role in the growing incidence of type 2 diabetes. We have previously shown that age, diet, birth weight, physical activity and genetic variation influence DNA methylation of candidate genes for type 2 diabetes in human skeletal muscle. We were further the first to demonstrate that DNA methylation plays a role in gene regulation in pancreatic islets from patients with type 2 diabetes. Nevertheless, our knowledge about the epigenetic mechanisms linking environmental factors and type 2 diabetes remains limited.
The overall objective of our research is to identify the key epigenetic mechanisms influencing the pathogenesis of T2D.
We are currently analysing DNA methylation in skeletal muscle, adipose tissue and pancreatic islets of a number of human cohorts. Here, we examine if non-genetic and genetic factors as well as type 2 diabetes affect epigenetic variation in human tissues (Figure 1). We are further relating DNA methylation to gene expression, in vivo metabolism and type 2 diabetes. Histone modifications are being analysed in clonal beta-cells and human pancreatic islets.
Last updated: January 19, 2012
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