Endocrine Abstracts

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...

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...

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...

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...

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...

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...