Endocrine Abstracts

The metastasis related methyltransferase 1 (Merm1), originally designated WBSCR22, is implicated in cancer through H3K9 methylation and silencing of the tumour-suppressor Zac1 gene. Activated GR is a transcription factor with chromatin remodelling activity, and so the functional interaction between GR, and Merm1 was determined. Merm1 consistently potentiated GR transactivation of TAT3-Luc in HeLa cells. This was dependent on the SAM and methyltransferase domains of Merm1. Merm...

Glucocorticoids (GCs) are potent anti-inflammatory agents, but a variable therapeutic response occurs. We have used microarray analysis to explore the basis for inter-individual differences in the GC sensitivity of a healthy volunteer population, and identified genes predictive of response to GCs. Three such discriminating genes were then selected to be investigated for their potential to interact with the Glucocorticoid Receptor (GR). These are the Bone Morphogenetic Protein ...

Rheumatoid arthritis (RA) is a common chronic systemic inflammatory disease. Several new therapies exist for RA but long-term patient management remains problematic.We have discovered that hypoxia, a characteristic of inflamed tissues, potently inhibits glucocorticoid (Gc) sensitivity. This effect is mediated, in part by HIF1α, whose activity is induced in hypoxia. HIF1α gene expression is also induced in primary peripheral blood mononuclear ce...

MIF is a potent pro-inflammatory mediator that opposes the anti-inflammatory actions of glucocorticoids (Gc) and is involved in the pathogenesis of multiple diseases. The MIF promoter is inhibited by Gc in lymphocytes (CEMC7A) but not in epithelial cells (A549), despite expression of functional glucocorticoid receptors (GR) in both. Deletion studies localized the cis element responsible for Gc inhibition to between MIF −71 and +85. This sequence contained no GR binding s...

Glucocorticoids (Gc) act on most cells and tissues, but their effects vary in a cell-type specific manner. A number of genes show divergent responses to glucocorticoid action, dependent on their tissue of origin. One such gene is MIF, a proinflammatory cytokine associated with Gc resistance in inflammation, and linked with susceptibility to chronic, human inflammatory disease. Importantly, MIF gene expression is inhibited by Gc in lymphoblasts, but not in epithelial cells; a f...

High IGF2 has been associated with longitudinal weight loss. We wished to study associations of genes coding for IGF2 and for binding proteins that have preferential IGF2 affinity (IGFBP2, IGFBP5 and IGFBP6) in 991 Caucasian subjects from Salford with type 2 diabetes.Fifteen IGF2, four IGFBP2, eight IGFBP5 and one IGFBP6 SNPs were successfully genotyped. Longitudinal BMI data for the years 2002 to 2009 was obtained fro...

Introduction: T2DM is one of the main causes of morbidity and mortality in the UK. Epigenetic mechanisms impact gene expression and could predispose individuals to a particular metabolic phenotype. We investigated association of LINE-1 methylation (a surrogate of global DNA methylation) with cardiometabolic parameters in a longitudinal cohort of T2DM patients.Methods: Global LINE-1 DNA methylation in blood-derived DNA samples from 795 (men 60%, women 40%...

Introduction: T2DM is one of the main causes of morbidity and mortality in the UK. Epigenetic mechanisms impact gene expression and could predispose individuals to a particular metabolic phenotype. We investigated association of LINE-1 methylation (a surrogate of global DNA methylation) with cardiometabolic parameters in a longitudinal cohort of T2DM patients.Methods: Global LINE-1 DNA methylation in blood-derived DNA samples from 795 (men 60%, women 40%...

Introduction: There is growing evidence of external factors modulating epigenetic modifications and their contribution to the development of obesity and T2DM. One of the epigenetic signatures is DNA methylation. We investigated whether a lifestyle intervention could influence DNA methylation of Brain derived neurotrophic factor (BDNF) in individuals with IGR, as BDNF is thought to play an important role in glucose metabolism.Methods: IGR participants (<e...

Background: The prevalence of obesity associated comorbidities, such as Type 2 Diabetes(T2D) and hypertension, continues to rise globally. Our study aimed to describe the long-term effects on blood pressure management in individuals with T2D post bariatric surgery in a single centre prospective observational cohort study in North-West England.Methods: We undertook a 10-year prospective cohort study on people who underwen...