Searchable abstracts of presentations at key conferences in endocrinology

ea0077p172 | Metabolism, Obesity and Diabetes | SFEBES2021

ATP-Binding Cassette Subfamily C Member 1 (ABCC1) influences adiposity, glucose homeostasis and insulin sensitivity

Villalobos Elisa , Chua EE June , Miguelez-Crespo Allende , Morgan Ruth , Andrew Ruth , Nixon Mark , Walker Brian

Background: Glucocorticoids (GCs) modulate glucose homeostasis by acting on metabolic tissues including liver, adipose, and skeletal muscle. ABCC1 is a transmembrane ‘drug-resistance’ transporter expressed in adipose tissue and skeletal muscle with previously unknown physiological function. We recently showed that ABCC1 modulates intracellular GC concentrations and action in adipose. Here, we tested the hypothesis that Abcc1 regulates GC concentrations in skeletal mu...

ea0086p331 | Metabolism, Obesity and Diabetes | SFEBES2022

Mass Spectrometry Imaging to Investigate Carnitine Metabolism during Brain Ageing

Khan Shazia , Andrew Ruth , Rattray Nicholas

Ageing is associated with decline in mitochondrial function whereby dysregulation in carnitine metabolism is highly correlated to poor ageing phenotypes. L-Carnitine transports activated long-chain fatty-acids (FAs) across mitochondrial membranes for β-oxidation and energy production. It is hypothesised that accumulation of long-chain FAs within cells is related to disordered transportation and reflects lower cellular energy upon ageing. Our global aim is to determine the...

ea0077lb11 | Late Breaking | SFEBES2021

Mass spectrometry imaging for simultaneous analysis of lipid biomarkers, lysophosphatidic acid (LPAs) and lysophosphatidyl choline (LPCs), in fibrotic liver tissue

Khan Shazia , Fallowfield Jonathan , Webster Scott , Andrew Ruth

Autotaxin (ATX) is a secreted enzyme that generates the lipid signalling molecule LPAs from LPCs. The ATX/lPA axis is strongly linked to fibrotic diseases and therapeutic inhibitors are in development. Assessing the balance of LPC/lPA in diseased target tissues is critical to inform pharmacokinetics/pharmacodynamics (PK-PD) and predict efficacy of ATX inhibitors in vivo. Mass spectrometry imaging (MSI) allows concomitant measurement of multiple molecules with histopat...

ea0038p406 | Steroids | SFEBES2015

Quantitative analysis of an adrenal steroid profile, canrenone, and mifepristone in plasma by triple quadrupole mass spectrometry

Kyle Catriona , Naredo Gregorio , Andrew Ruth , Walker Brian , Homer Natalie

Canrenone and mifepristone (RU486) are respectively mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) antagonists commonly used to block or displace steroid for clinical pharmacological or research purposes. The aim of this study was to develop and validate a sensitive, quantitative assay for the combined analysis of glucocorticoids (cortisol, cortisone, corticosterone, and 11-dehydrocorticosterone), mineralocorticoids (aldosterone), canrenoate, and mifepristone...

ea0031p330 | Steroids | SFEBES2013

Quantitative analysis of canrenone in plasma by triple quadrupole mass spectrometry

Homer Natalie , Harrison Jill , Iqbal Javaid , Walker Brian , Andrew Ruth

Canrenone is a mineralocorticoid receptor antagonist used as a diuretic agent to treat hypertension. It is the major active metabolite of spironolactone and may be quantified in clinical studies either to ensure compliance or to gain information about pharmacokinetic-pharmacodynamic interactions.The aim of this study was to develop and validate a sensitive, quantitative assay for the analysis of canrenone in plasma.HPLC mass spectr...

ea0028p23 | Clinical biochemistry | SFEBES2012

A method for simultaneous analysis of androgens, dutasteride and finasteride in human serum by liquid chromatography tandem mass spectrometry

Upreti Rita , Homer Natalie , Naredo Gregorio , Walker Brian , Andrew Ruth

Background: 5α-Reductase (5αR) catalyses conversion of testosterone to its more potent metabolite dihydrotestosterone (DHT) and is inhibited when treating benign prostatic hyperplasia. 5αR has two isozymes; dual isozyme inhibition with dutasteride gives greater DHT suppression than finasteride, which inhibits only 5αR type 2.Aim: To develop a novel assay to simultaneously analyse testosterone, epitestosterone, DHT, androstenedione, du...

ea0028p305 | Steroids | SFEBES2012

Ageing and social isolation increase susceptibility to anxiety in mice lacking 5α-reductase type 1

Di Rollo Emma , Livingstone Dawn , Walker Brian , Andrew Ruth

Glucocorticoid excess is associated with increased anxiety and accelerated cognitive decline. Concentrations of glucocorticoids within tissues, including the brain, are influenced by local metabolism. 5α-Reductase 1 (5αR1), expressed in brain, converts corticosterone to its A-ring reduced metabolites, which have a different spectrum of activities. Here, we investigated if mice homozygous for disrupted 5αR1 alleles (5αR1-KO) experience heightened anxiety and...

ea0025oc2.2 | Steroids | SFEBES2011

Anti-inflammatory mechanisms of 5α-reduced glucocorticoids: potential dissociated steroids

Nixon Mark , Yang Chenjing , Rossi Adriano , Walker Brian , Andrew Ruth

We recently showed that 5α-reduced metabolites of corticosterone (B), namely 5α-dihydrocorticosterone (5αDHB) and 5α-tetrahydrocorticosterone (5αTHB), possess similar anti-inflammatory properties to B, but have lesser metabolic effects. Here, we explored the anti-inflammatory mechanisms of these 5α-reduced metabolites in vitro. Data are mean % suppression/induction, compared by one way ANOVA, *P<0.05 versus vehicle.<p class="...

ea0021oc1.3 | Diabetes and metabolism | SFEBES2009

Adipose-specific knockout of androgen receptors in mice results in hyperinsulinaemia without obesity

McInnes Kerry , Smith Lee , Saunders Philippa , Andrew Ruth , Walker Brian

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...

ea0021p187 | Diabetes and metabolism | SFEBES2009

Down-regulation of adipose 11βHSD1 mediates the insulin sensitising effects of salicylate in obesity

Nixon Mark , Livingstone Dawn , Andrew Ruth , Walker Brian

Anti-inflammatory salicylates improve insulin sensitivity, however the mechanism remains unclear. We have observed down-regulation of the glucocorticoid regenerating enzyme 11β-hydroxysteroid dehydrogenase 1 (11βHSD1) by salicylates in cultured adipocytes and in human adipose tissue after oral salsalate therapy, consistent with known transcriptional regulation of 11βHSD1 by pro-inflammatory cytokines. Since inhibition of 11βHSD1 improves insulin sensitivity...