GPR162 is a beta cell CART receptor.

Cocaine and amphetamine-regulated transcript (CART) is expressed in pancreatic islet cells and neuronal elements. We have previously established insulinotropic actions of CART in human and rodent islets. The receptor for CART in the pancreatic beta cells is unidentified.

SCRT1 is a novel beta cell transcription factor with insulin regulatory properties.

Here we show that scratch family transcriptional repressor 1 (SCRT1), a zinc finger transcriptional regulator, is a novel regulator of beta cell function. SCRT1 was found to be expressed in beta cells in rodent and human islets. In human islets, expression of SCRT1 correlated with insulin secretion capacity and the expression of the insulin (INS) gene.

Prominent action of butyrate over β-hydroxybutyrate as histone deacetylase inhibitor, transcriptional modulator and anti-inflammatory molecule.

Butyrate and R-β-hydroxybutyrate are two related short chain fatty acids naturally found in mammals. Butyrate, produced by enteric butyric bacteria, is present at millimolar concentrations in the gastrointestinal tract and at lower levels in blood; R-β-hydroxybutyrate, the main ketone body, produced by the liver during fasting can reach millimolar concentrations in the circulation. Both molecules have been shown to be histone deacetylase (HDAC) inhibitors, and their administration has been associated to an improved metabolic profile and better cellular oxidative status, with butyrate inducing PGC1α and fatty acid oxidation and R-β-hydroxybutyrate upregulating oxidative stress resistance factors FOXO3A and MT2 in mouse kidney.

The histone deacetylase inhibitor sodium butyrate improves insulin signalling in palmitate-induced insulin resistance in L6 rat muscle cells through epigenetically-mediated up-regulation of Irs1.

Dietary administration of the histone deacetylase (HDAC) inhibitor butyric acid - a short chain fatty acid present in milk products and also bacterially produced in the intestine - has been shown to increase energy expenditure and favour insulin sensitivity in mice through induction of PGC1α (peroxisome proliferator-activated receptor gamma co-activator 1α) and AMPK (AMP-activated protein kinase) in skeletal muscle, and a consequential increase of mitochondrial fatty acid oxidation. Here, we investigate whether such physiological improvements are associated to epigenetic effects dependent on increased histone acetylation and whether butyrate exerts a direct action on skeletal muscle insulin signalling. We show that sodium butyrate (NaBut) ameliorates the insulin-resistant phenotype, induced in L6 myotubes by prolonged exposure to palmitate, by i) increasing the insulin-induced phosphorylation of both PKB (protein kinase B) and MAPK (mitogen activated protein kinase), the two branches of insulin signalling and ii) increasing histone H3 acetylation - even in the presence of palmitate - on chromatin in proximity of the Irs1 (insulin receptor substrate 1) transcriptional start site.

[Epigenetics in transgenerational responses to environmental impacts: from facts and gaps].

The existence of non-genetic and non-cultural mechanisms that transfer information on the memory of parental exposures to various environments, determining the reactivity of the following generations to their environments during their life, are of growing interest. Yet fundamental questions remain about the nature, the roles and relative importance of epigenetic marks and processes, non-coding RNAs, or other mechanisms, and their persistence over generations. A model incorporating the various transmission systems, their cross-talks and windows of susceptibility to the environment as a function of sex/gender of parent and offspring, has yet to be built.