Searchable abstracts of presentations at key conferences in endocrinology

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...

ea0028oc4.3 | Steroid | SFEBES2012

A hypomorphic H6PD allele is sufficient to rescue the skeletal myopathy but not the lack of 11β-HSD type 1-mediated glucocorticoid regeneration phenotypes of H6PDKO mice

Zielinska Agnieszka , Doig Craig , McCabe Emma , Stewart Paul , Lavery Gareth

In the endo/sarcoplasmic reticulum (ER/SR), hexose-6-phosphate dehydrogenase (H6PDH) generates an NADPH/ NADP ratio sufficient to drive 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)-mediated glucocorticoid (GC) activation (11-DHC to corticosterone). In H6PDH knockout (H6PDKO) mice a reduced NADPH/NADP ratio leads to reversed 11β-HSD1 activity (corticosterone to 11-DHC), and GC insensitivity. They also display skeletal myopathy driven by activation of the un...

ea0034p266 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2014

Breaking NAD+: investigating NMRK2 as a regulator of muscle adaptation through NAD+ salvage

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

Exercise has undisputed health benefits mediated through metabolic adaptation in skeletal muscle. In contrast, a sedentary lifestyle, leads to impaired metabolic function and negative health outcomes such as insulin resistance and sarcopenia. Whilst exercise improves skeletal muscle metabolism, how the process is co-ordinated at a cellular level remains unclear. Recently, NAD+ has been suggested to play an important role in muscle adaptation, acting as a substrate f...

ea0034p267 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2014

11β HSD1KO mice resist aged associated decline in markers of brown adipose tissue function

McCabe Emma , Doig Craig , Morgan Stuart , Larner Dean , Tomlinson Jeremy , Stewart Paul , Lavery Gareth

The primary function of brown adipose tissue (BAT) is to use lipids to generate heat through uncoupling of oxidative phosphorylation in mitochondria. Glucocorticoids (GC) have a negative effect upon BAT through inhibition of uncoupling protein 1 (UCP1) expression. Similarly, it has been reported that BAT levels decline with age and have been linked to age related accumulation of body fat, leading to the idea that improving BAT function during ageing could have a beneficial rol...

ea0034oc3.1 | Steroids | SFEBES2014

Lack of 11β-hydroxysteroid dehydrogenase type 1 ameliorates the adverse features of Cushing's syndrome

Morgan Stuart , McCabe Emma , Gathercole Laura , Hassan-Smith Zaki , Larner Dean , Bujalska Iwona , Stewart Paul , Tominson Jeremy , Lavery Gareth

Glucocorticoids are widely prescribed for their anti-inflammatory properties, but have a significant adverse effect profile, leading to a Cushingoid phenotype. In the present study, we test the hypothesis that reactivation of glucocorticoids, in peripheral tissues by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), is a major determinant of exogenous Cushing’s syndrome.WT, global 11β-HSD1 knockout (GKO), liver-specific 11β-HSD...