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...

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an NADPH-dependant oxo-reductase located in the sarcoplasmic reticulum (SR) lumen of skeletal muscle. It generates active glucocorticoids to regulate permissive and adaptive metabolism. Hexose-6-phosphate dehydrogenase (H6PD) interacts with 11β-HSD1 to generate an appropriate NADPH/NADP+ ratio to support activity. H6PD depletion impairs SR NADPH generation triggering 11β-HSD1 to assume glucocorticoid ina...

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an NADPH-dependant oxo-reductase located in the sarcoplasmic reticulum (SR) lumen of skeletal muscle. It generates active glucocorticoids to regulate permissive and adaptive metabolism. Hexose-6-phosphate dehydrogenase (H6PD) interacts with 11β-HSD1 to generate an appropriate NADPH/NADP+ ratio to support activity. H6PD depletion impairs SR NADPH generation triggering 11β-HSD1 to assume glucocorticoid ina...

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an NADPH-dependant oxo-reductase located in the sarcoplasmic reticulum (SR) lumen of skeletal muscle. Here it generates active glucocorticoids to regulate permissive and adaptive metabolism, and can mediate the pathological effects of glucocorticoid excess. Hexose-6-phosphate dehydrogenase (H6PD) in the SR interacts with 11β-HSD1 to generate an appropriate NADPH/NADP+ ratio to support activity. H6PD depletion...

Nicotinamide adenine dinucleotide (NAD+) levels increase during metabolic stress, which acts as a consumed substrate by, amongst other proteins, the sirtuins, which adapt transcriptional programmes to increase energy availability and regulate insulin sensitivity. Thus, maintaining appropriate skeletal muscle NAD+ availability is critical for regulating systemic energy homeostasis. In order to gain better insight into ageing muscle NAD+ dynamics we used ta...

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 decline in skeletal muscle nicotinamide adenine dinucleotide (NAD+) can decrease mitochondrial function and energy metabolism in age-related metabolic disease. Restoration of NAD+ using the precursor nicotinamide riboside (NR) may serve to support age and disease driven impairment of mitochondrial energy metabolism. Manipulating NAD+, and consequently cellular pyridine nucleotide NAD(P)(H) pools, may impact the flux of glucose through intermediary energy metabolism pathways....

Metastasis is a multistep process responsible for the vast majority of endocrine cancer deaths. We have previously identified the proto-oncogene PBF to be upregulated in differentiated thyroid cancer, and recently PBF expression has been correlated with distant thyroid cancer metastasis at diagnosis. Further, PBF potently induces breast cancer cell invasion in vitro, and our recent in vivo data demonstrate that colorectal tumours with higher PBF protein expre...

Background and Aim: Supplementation with precursors of nicotinamide adenine dinucleotide (NAD), was shown to be beneficial in preventing metabolic dysfunction in mice, which is induced by feeding a high fat diet. We compared the effect of nicotinamide riboside (NR) supplementationon whole-body energy metabolism and mitochondrial function in two widely used diet-induced obesity mouse models.Methods: Mice were fed a high fat diet (HFD, 60% fat) or standard...