Endocrine Abstracts

Introduction: Accumulating evidence suggests a role for IGF1 in insulin resistance and cardiovascular disease. IGF1 enhances glucose uptake and nitric oxide (NO) production, via similar mechanisms to insulin. Previously we have reported a mouse model with global heterozygous knockout of the IGF1 receptor (IGF1RKO) that has enhanced insulin sensitivity and increased nitric oxide (NO) production in the vasculature.Methods: To investigate this further we us...

Maternal undernutrition influences the development of obesity and diabetes in the adult offspring. Previous work has shown that moderate maternal undernutrition may alter the stress–response of the hypothalamic–pituitary–adrenal (HPA) axis; however, it is not clear if this is the mechanism for consequent obesity in offspring.The aim of this study was to analyse epigenetic changes in the POMC and GR genes in the pituitary as markers of HPA ...

Background: Visceral fat is a key factor underlying type 2 diabetes. The amount and distribution of body fat is strongly influenced by sex steroids. Androgen receptors (ARs) are present in adipose tissue and are abundant in the detrimental visceral bed. Here, we sought to determine the contribution of the AR in adipose tissue to the pathophysiology of visceral obesity and type 2 diabetes.Methods: Male fat-specific AR-knockout (fARKO) mice (12 weeks; n...

Chronic elevation of saturated fatty acids (SFAs) and glucose (Glc) appears to activate an inflammatory response; compounded by habitual feeding. Restoration of physiological SFAs and Glc levels post-prandially may not attenuate the original insult; a concept termed ‘metabolic memory’. Therefore we investigated (1) the effect of chronic and oscillating SFAs and Glc on the inflammatory pathway in human abdominal subcutaneous (AbdSc) adipose tissue (AT) and adipocytes ...

The anti-inflammatory protein, annexin 1 (ANXA1) acts via a formyl peptide receptor (FPR), possibly FPR2, in the neuroendocrine system to mediate feedback effects of glucocorticoids and thereby modulate the HPA responses to immune insults. Here, we explored further the role of ANXA1 and the FPR family in mediating the HPA responses to endotoxin (LPS), focusing on the adrenal cortex.Adult male mice treated with LPS (500 μg/kg, i.p.) showed time-depen...

Hypogonadism is a common finding in men with metabolic syndrome (MS) and/or type 2 diabetes (T2D) which adversely affects quality of life, is associated with several cardiovascular (CV) risk factors and a greater risk of mortality. Testosterone replacement therapy (TRT) in pilot studies has beneficial effects on waist circumference (WC), insulin resistance, glycaemic control, lipid and inflammatory profiles.Testosterone replacement in hypogonadal metabol...

Glucocorticoid (GC) production rates are elevated in obese, insulin resistant individuals. We and others have demonstrated decreased hepatic cortisol regeneration through reduced 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity that converts inactive cortisone to cortisol. In addition, there is enhanced cortisol clearance by A-ring reductases, (notably 5α-reductase). We have argued that these changes drive the hypothalamo-pituitary–adrenal axis a...

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. The role of glucocorticoids (GC) in its pathogenesis, is highlighted in patients with GC excess, Cushing’s syndrome, who develop central adiposity, insulin resistance and in 20% of cases, NAFLD. Although circulating cortisol levels are normal in patients with NAFLD, hepatic cortisol availability is controlled by enzymes that regenerate cortisol from inactive cortisone (11&#94...