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...

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...

ea0028oc4.3 | 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...

ea0037ep389 | Diabetes (pathiophysiology & epitemiology) | ECE2015

Increasing NAD+ availability in skeletal muscle to augment energy metabolism

Fletcher Rachel , Doig Craig , Zielinska Agnieszka , Griffin Aliesha , Philp Andrew , Lavery Gareth

NAD+, an essential coenzyme in energy production, has recently risen to prominence as a signalling molecule central in mediating cellular metabolism and mitochondrial function. NAD+ dependent protein deacetylase sirtuin (SIRT) proteins regulate key metabolic transcription factors, including FOXOs and PGC-1α in muscle, in response to cellular energy demands and metabolic stress. Declining NAD+, metabolic and mitochondrial function are hallm...

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...

ea0028p304 | Steroids | SFEBES2012

HSD11B1 promoter binding of the NF-κB p65 subunit in response to TNF-α suppresses 11β-HSD1 expression and activity in C2C12 muscle cells

Doig Craig , Bashir Jamila , Zielinska Agnieszka , Cooper Mark , Stewart Paul , Lavery Gareth

A counter-regulatory rise in GC levels is important to the inflammatory response, that when impaired is associated with high mortality in inflammatory states. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerate’s intracellular glucocorticoids (GC), amplifying their actions, and has been postulated to play a role in the development of inflammation-associated arthritis, obesity and myopathy. Pro-inflammatory cytokines (e.g. TNF-α) increase expressio...