The co-activator-associated arginine methyltransferase 1 (CARM1) gene is overexpressed in type 2 diabetes.

Purpose: We examined the expression of a panel of epigenetic enzymes catalyzing histone tails post-transcriptional modifications, together with effectors of metabolic and inflammatory alterations, in type 2 diabetes.

Methods: Cross-sectional, case-control study of 21 people with type 2 diabetes and 21 matched controls. Total RNA was extracted from white cells and reverse transcribed.

High-fat diet unveils an enhancer element at the Ped/Pea-15 gene responsible for epigenetic memory in skeletal muscle.

Background: The impact of nutrition on the evolution towards type 2 diabetes has recently received increasing attention because of the effect on chromatin structure and gene expression.

Purpose: Evaluate the effect of high-fat diet on chromatin remodelling and expression of Ped/Pea-15, a gene commonly overexpressed in individuals at risk of type 2 diabetes.

Methods: We used mouse and cell models to investigate Ped/Pea-15 transcriptional regulation by high-fat diet and glucose, respectively.

Glucose-induced expression of the homeotic transcription factor Prep1 is associated with histone post-translational modifications in skeletal muscle.

Aims/hypothesis: Chronic hyperglycaemia worsens insulin resistance in individuals with type 2 diabetes. Whether this effect is contributed by epigenetic dysregulation and which genes are involved remain unclear. Prep1 (also known as Pknox1) is a gene exerting major effects on the sensitivity of the glucose transport machinery to insulin.

Dietary polyphenols and chromatin remodeling.

Polyphenols are the most abundant phytochemicals in fruits, vegetables, and plant-derived beverages. Recent findings suggest that polyphenols display the ability to reverse adverse epigenetic regulation involved in pathological conditions, such as obesity, metabolic disorder, cardiovascular and neurodegenerative diseases, and various forms of cancer. Epigenetics, defined as heritable changes to the transcriptome, independent from those occurring in the genome, includes DNA methylation, histone modifications, and posttranscriptional gene regulation by noncoding RNAs.

Understanding type 2 diabetes: from genetics to epigenetics.

The known genetic variability (common DNA polymorphisms) does not account either for the current epidemics of type 2 diabetes or for the family transmission of this disorder. However, clinical, epidemiological and, more recently, experimental evidence indicates that environmental factors have an extraordinary impact on the natural history of type 2 diabetes. Some of these environmental hits are often shared in family groups and proved to be capable to induce epigenetic changes which alter the function of genes affecting major diabetes traits.

Peroxisome proliferator-activated receptor-γ activation enhances insulin-stimulated glucose disposal by reducing ped/pea-15 gene expression in skeletal muscle cells: evidence for involvement of activator protein-1.

The gene network responsible for inflammation-induced insulin resistance remains enigmatic. In this study, we show that, in L6 cells, rosiglitazone- as well as pioglitazone-dependent activation of peroxisome proliferator-activated receptor-γ (PPARγ) represses transcription of the ped/pea-15 gene, whose increased activity impairs glucose tolerance in mice and humans. Rosiglitazone enhanced insulin-induced glucose uptake in L6 cells expressing the endogenous ped/pea-15 gene but not in cells expressing ped/pea-15 under the control of an exogenous promoter.