Searchable abstracts of presentations at key conferences in endocrinology

ea0044pl3 | Society for Endocrinology Starling Medal Lecture | SFEBES2016

Breaking NAD+: Vitamin B3 salvage and metabolism in metabolic health

Lavery Gareth

NAD+, as well as its phosphorylated form NADP+, are best known as electron carriers and co-substrates of various redox reactions essential to the cellular processes of energy metabolism and biosynthesis. Dynamic changes in NAD+ availability can trigger sensors, such as the protein deacetylase sirtuin enzymes, to adjust cellular and tissue physiology in response to changes in nutrient availability and energy demand. These signalling processes consume NAD+ and release nicotinami...

ea0037s14.3 | Adipose tissue as an endocrine organ (<emphasis role="italic">Endorsed by Endocrine Connections</emphasis>) | ECE2015

Manipulating adipose tissue sensitivity to glucocorticoid excess

Lavery Gareth

Glucocorticoids (GCs) have physiological actions in almost all tissues, classically mediated by the GC receptor. The potent effects of GCs upon metabolic phenotype are best exemplified in patients with circulating GC excess (Cushing’s syndrome), who develop central (visceral) obesity, insulin resistance, myopathy, hypertension and in some cases overt type 2 diabetes (T2DM) and non alcoholic fatty liver disease (NAFLD). GCs are one of the most frequently prescribed class o...

ea0031ye1.1 | Maintaining your endocrine career despite what life throws at you | SFEBES2013

Maintaining an active basic research career whilst juggling an academic and personal life

Lavery Gareth

We all want to be earnest and successful basic researchers; usually this means running a group and this can be difficult when as an academic you will also have administrative duties, committees to attend and teaching to give. And as a rounded and fulfilled human being you will have a personal life that rewards in many other ways, such as a passion for sport, family or other activities. Life is and should be fluid, so it is unrealistic and unrewarding to schedule an equal numbe...

ea0013oc5 | Society for Endocrinology/Clinical Endocrinology Trust Young Investigator Basic Prize winner | SFEBES2007

Hexose-6-phosphate dehydrogenase: A novel regulator of glucocorticoid hormone action

Lavery Gareth

The novel congenital adrenal hyperplasia variant, ‘apparent’ cortisone reductase deficiency (ACRD), has highlighted the significance of subcellular redox potential in regulating glucocorticoid hormone action. In ACRD, there is an attenuation of perceived glucocorticoid (GC) concentrations which results in up-regulation of adrenal androgen production as a consequence of increased hypothalamic-pituitary-adrenal (HPA) activity. We have recently identified mutations in t...

ea0094p156 | Adrenal and Cardiovascular | SFEBES2023

Glucocorticoid receptor and PARP-1 genomic binding changes in response to corticosterone excess in mice

Heaselgrave Samuel , Lavery Gareth , Doig Craig

Ligand binding of the glucocorticoid receptor (GR) initiates recruitment to GR Response Elements (GRREs). GR transcriptional activation of genes manifests many of the pleiotropic actions attributed to glucocorticoids. However, excessive exposure to GCs produces detrimental impacts, shifting GR behaviour and driving dysregulated metabolic states. Moreover, GR, its interacting partners, and influencing proteins remain ambiguous. Poly-(ADP-ribosyl) polymerase 1 (PARP1) is a chrom...

ea0077p198 | Metabolism, Obesity and Diabetes | SFEBES2021

Corticosterone excess alters metabolic rate in male and female C57BL/6J mice

Heaselgrave Samuel , Heising Silke , Morgan Stuart , Morton Nicholas , Lavery Gareth

Introduction: Glucocorticoids are vital for regulating metabolic processes, as well as use in medical treatments. However chronic glucocorticoid excess is known to cause negative metabolic effects including hyperglycaemia, muscle atrophy and fat accumulation. The effect on energy metabolism and metabolic rate remains undefined and merits investigation in both male and female mice.Methods: 20 male and 20 female C57BL/6J mice were randomly assigned to a co...

ea0059oc5.3 | Adrenal | SFEBES2018

11βHSD1 mediates therapeutic glucocorticoid-induced muscle atrophy in chronic inflammatory disease

Webster Justine , Fenton Chloe , Lavery Gareth , Langen Ramon , Hardy Rowan

Objective: Therapeutic glucocorticoids (GCs) are commonly used in the treatment of chronic inflammatory disease. Unfortunately, their long-term administration is associated with deleterious systemic side effects including muscle atrophy. 11 beta-hydroxysteroid dehydrogenase type 1 (11βHSD1) activates glucocorticoids within muscle, is increased with inflammation, and has previously been shown to mediate GC induced muscle wasting. We examined the role of 11 beta-hydroxyster...

ea0034p265 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2014

Depletion of glucose-6-phosphate transporter impacts SR calcium homeostasis in muscle

Doig Craig , Zielinska Agnieszka , Fletcher Rachel , McCabe Emma , Lavery Gareth

Glycogen storage disease type 1b is a metabolic disorder resulting in an inability to shuttle glucose-6-phosphate across the sarcoplasmic/endoplasmic reticulum (SR/ER) lumen. Mutation of the SoLute Carrier 37a4 (slc37a4) or glucose-6-phosphate transporter (G6PT) gene responsible for the distribution of G-6-P across this membrane leads to, hypoglycemia, hepatic glycogen accumulation, hyperlipidemia, resulting in life-limiting outcomes including growth retardation and neutropeni...

ea0034p268 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2014

H6PDH deficiency in muscle impacts amino acid metabolism

Zielinska Agnieszka , Doig Craig , Stewart Paul , Adamski Jerzy , Lavery Gareth

Hexose-6-phosphate dehydrogenase is an important factor in setting the redox status of the endo-/sarcoplasmic reticulum (ER/SR) lumen by generating the NADPH:NADP+ ratio for 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) mediated glucocorticoid (GC) activation. H6PDH knockout mice (H6KO) clearly demonstrate the obligate nature of 11β-HSD1 for H6PDH, and display a vacuolating of type IIb fiber myopathy, elevated glycogen storage and type II to type...

ea0028oc4.1 | Steroid | SFEBES2012

Increased 11β-hydroxysteroid dehydrogenase type 1 activity is associated with the adverse expression of glucocorticoid target genes in ageing human skin

Tiganescu Ana , Walker Elizabeth , Cooper Mark , Lavery Gareth , Stewart Paul

Glucocorticoid (GC) excess adversely affects many aspects of skin homeostasis, characteristics of which are also seen during ageing (e.g. poor wound healing). The mechanisms underlying this remain unclear. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates cortisol, independently of circulating concentrations, and we have previously demonstrated increased 11β-HSD1 expression in human dermal fibroblasts (HDF) from aged donors. We have now e...