Searchable abstracts of presentations at key conferences in endocrinology

ea0081rc10.3 | Rapid Communications 10: Diabetes, Obesity, Metabolism and Nutrition 3 | ECE2022

Primary bile acids differentially regulate differentiation of human abdominal and gluteal pre-adipocytes

Sabaratnam Rugivan , da Conceicao Ismael , Loh Nellie , Christodoulides Constantinos , Karpe Fredrik , Tomlinson Jeremy , Nikolaou Nikolaos

Bile acids (BAs) are synthesised from cholesterol in the liver and promote lipid digestion. An emerging body of evidence, however, suggests that BAs are also key signaling molecules with potent metabolic and endocrine functions, exerting their effects through activation of BA receptors, including the farnesoid-X- (FXR) and the G-protein-coupled- (TGR5) receptors. Disturbed BA synthesis has been associated with type 2 diabetes mellitus and insulin resistance, and recent studies...

ea0081p370 | Diabetes, Obesity, Metabolism and Nutrition | ECE2022

Differential localisation of the A-ring reductases in human hepatocytes: implications for substrate preference and utilisation

Potter Tom , da Conceicao Ismael , Nikolaou Nikolaos , Loh Nellie , Tomlinson Jeremy , Gathercole Laura

The 5-reductases are steroid metabolising enzymes that saturate the C4=C5 bond of the steroid A-ring, and their substrates include androgens, glucocorticoids, and bile acids. 5β-reductases (SRD5A1 & SRD5A2) convert testosterone to the more potent androgen 5β-dihydrotestosterone, and carry out the first step in glucocorticoid clearance, generating 5β-dihydrocortisol from cortisol. 5β-reductase (AKR1D1) is also able to carry out the first step of glucocor...

ea0025p136 | Diabetes, metabolism and cardiovascular | SFEBES2011

The Megalin-Cubilin receptor-mediated endocytic pathway is impaired in Dent's disease renal proximal tubule cell-lines

Gorvin Caroline , Wilmer Martijn , Loh Nellie , Piret Sian , Harding Brian , van den Heuvel Lambertus , Levtchenko Elena , Thakker Rajesh

Receptor-mediated endocytosis (RME), involving megalin and cubilin, mediates renal proximal-tubular reabsorption of glucose, proteins and hormones including insulin, parathyroid-hormone and vitamin D. RME disruption occurs in Dent’s disease patients with mutations of the chloride/proton antiporter, CLC-5, who suffer from low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis and renal failure. To further investigate the RME role of CLC-5 we established conditio...

ea0013p149 | Diabetes, metabolism and cardiovascular | SFEBES2007

Metabolic cage studies reveal that mice require 5 days for acclimatisation: establishing normal urinary and blood biochemistry values in BALB/c and C3H/HeH inbred mouse strains

Stechman Michael , Ahmad Bushra , Loh Nellie , Reed Anita , Hough Tertius , Bentley Liz , Cox Roger , Brown Steve , Thakker Rajesh

Inbred laboratory mice are widely used to generate, by homologous recombination, transgenic and chemical mutagenesis routes, genetic models of human disease. However, physiological studies of such models are hampered by the lack of normal ranges for serum and urinary biochemistry, particularly in relation to acclimatisation following placement in metabolic cages. To establish such values, we investigated urinary and serum parameters in forty, 24–30 week-old C3H/HeH, BALB/...

ea0021p19 | Bone | SFEBES2009

Hereditary renal calcification locus, Rcalc1, is associated with altered expression of cell survival genes

Loh Nellie Y , Stechman Michael J , Schulz Herbert , Jeyabalan Jeshmi , Reed Anita A C , Ahmad Bushra , Stewart Michelle , Brown Steve D M , Huebner Norbert , V. Thakker Rajesh

Renal stone disease is a common disorder for which the underlying causes remain largely unknown. We have investigated a hereditary renal calcification mouse model, Rcalc1, that is not associated with hypercalciuria for underlying mechanisms. Kidney RNA from 30 to 33 week-old Rcalc1 and control BALB/c and C3H female mice (n=4/group) was extracted and hybridised to Mouse Genome 430 2.0 arrays (Affymetrix). Following Robust Multichip Average normalization, pair-wise compar...

ea0021p21 | Bone | SFEBES2009

Transient receptor potential cation channel, subfamily Vanilloid, member 5 (Trpv5) mutation (Ser682Pro) results in loss of apical membrane expression in the distal convoluted tubule, thereby resulting in hypercalciuria

Loh Nellie Y , Dimke Henrik , Bentley Liz , Tammaro Paolo , Hough Tertius , Cox Roger D , Brown Steve D M , Ashcroft Frances M , Hoenderop Joost , Bindels Rene , Thakker Rajesh V

Transient receptor potential cation channel, subfamily Vanilloid, member 5 (TRPV5) is a member of the TRP superfamily. TRPV5, which functions as a tetramer, is localized to apical membranes of distal convoluted tubules (DCT) and connecting tubules (CNT) of the kidney, and is involved in vitamin D-regulated calcium reabsorption. Mice with a targeted deletion of Trpv5 (Trpv5−/−) develop severe hypercalciuria, compensatory hyperabsorption of dietary ...

ea0021p23 | Bone | SFEBES2009

A mouse model of early-onset renal failure, tertiary hyperparathyroidism and renal osteodystrophy

Esapa Chris , Head Rosie , Di Pretoro Simona , Crane Elisabeth , Loh Nellie , Devuyst Olivier , Thomas Gethin , Brown Steve , Brown Matt , Croucher Peter , Cox Roger , Thakker Rajesh

Abnormalities of calcium homeostasis such as secondary or tertiary hyperparathyroidism, and renal osteodystrophy often occur in patients with kidney failure. However, investigations of the underlying molecular mechanisms have been hampered by the lack of available tissues from patients and the lack of suitable animal models. We therefore sought to overcome this limitation by investigating mice treated with the chemical mutagen N-ethyl-N-nitrosourea and identified...

ea0013p140 | Diabetes, metabolism and cardiovascular | SFEBES2007

cDNA expression profiling studies reveal 7 differentially expressed genes on mouse chromosome 7 that may influence renal calcification in C3H/HeH inbred mice

Loh Nellie , Stechman Michael , Reed Anita , Ahmad Bushra , Stewart Michelle , Hacker Terry , Schulz Herbert , Born Gabi , Dear Neil , Brown Steve , Hubner Norbert , Thakker Rajesh

Vascular calcification, occurring in organs such as heart and kidneys, is associated with increased risk of cardiovascular mortality. The underlying molecular mechanisms remain unknown. To elucidate these, we investigated C3H mice, an inbred strain susceptible to vascular, myocardial and renal calcification. Myocardial calcification in C3H mice involves 4 genetic loci, Dyscalc1-4, that map to chromosomes 7, 4, 12 and 14, respectively. Dyscalc1 contributes to myoc...

ea0034oc4.6 | Thyroid and bone | SFEBES2014

An ENU-induced Tyr265Stop mutation in Polg2 is associated with renal calcification in RCALC2 mice

Gorvin Caroline , Piret Sian , Ahmad Bushra , Stechman Michael , Loh Nellie , Hough Tertius , Leo Paul , Marshall Mhairi , Sethi Siddharth , Bentley Liz , Reed Anita , Christie Paul , Simon Michelle , Mallon Ann-Marie , Brown Matthew , Cox Roger , Brown Steve , Thakker Rajesh

Renal calcification (nephrocalcinosis), which has a multi-factorial etiology involving environmental and genetic determinants, affects ~8% of adults by 70 years. Nephrocalcinosis may occur as a familial disorder in ~65% of patients, and in 70% of patients, nephrocalcinosis may be associated with endocrine and metabolic disorders that include primary hyperparathyroidism, renal tubular acidosis, hypercalciuria, cystinuria, and hyperoxaluria. Investigations of families with hered...

ea0015oc37 | Thyroid | SFEBES2008

Endocytosis involves a CLC-5 and KIF3B interaction: relevance to thyroid and renal tubular function

Reed Anita AC , Loh Nellie , Lippiat Jonathan , Partridge Chris , Galvanovskis Juris , Williams Sian , Jouret Francois , Wu Fiona , Courtoy Pierre , Nesbit M Andrew , Devuyst Olivier , Rorsman Patrik , Ashcroft Frances , Thakker Rajesh V

Endocrine cells utilise endocytosis to scavenge polypeptide hormones, and to generate signals from inactive precursors, such as release of thyroid hormones from thyroglobulin in thyrocytes, and activation of vitamin D after reabsorption of ultrafiltrated pro-vitamin D binding protein complex by renal proximal tubular cells (PTC). We have investigated the role of CLC-5, a chloride/proton antiporter expressed in apical endosomes and the apical plasma membrane of thyrocytes and P...