Endocrine Abstracts

Introduction: The clinical features and complications of Cushing’s syndrome result from chronic excess of circulating cortisol, typically quantified by 24-h urinary free cortisol (UFC). LCI699 is a potent inhibitor of 11β-hydroxylase. Since 11β-hydroxylase catalyzes the final step of cortisol synthesis, LCI699 is a potential new treatment for all forms of Cushing’s syndrome.Methods: Adult patients with mild-to-severe Cushing’s di...

Objective: To determine if autologous nonmyeloablative hematopoietic stem cell transplantation (AHSCT) was worthwhile to do in type 1 diabetes adolescents with diabetic ketoacidosis at diagnosis.Research Design and Methods: We enrolled 28 type 1 diabetes patients aged 14–30 years in a prospective AHSCT phase II clinical trial. Hematopoietic stem cells were harvested from the peripheral blood following a pretreatment consisting of a combination of cy...

Cancer cells have shown an overexpressed fructose transporter GLUT5 and preferential utilization of fructose as compared to glucose, implicating that a fructose-based analogue would be a useful target for diagnosis and treatment of cancer. We have successfully synthesized the fructose conjugated-gefitinib compounds {N-[4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-7-methoxy-quinazolin-6-yl]-4- [N-methyl-N-(1-deoxy-1-fructosyl)]aminobutanamide}, and examined its antitumor effic...

The calcium-sensing receptor (CaSR) is a G protein-coupled receptor with an extracellular bilobed venus flytrap domain (VFTD) predicted to contain five calcium-binding sites. The major site for calcium-binding is comprised of amino acid residues that line the cleft between the two lobes of the VFTD. We investigated the structure-function relationships of VFTD CaSR mutations identified in patients with familial hypocalciuric hypercalcaemia (FHH), neonatal severe primary hyperpa...

Background: Millions of people worldwide take an intentional nap or siesta after lunch, but data describing potential health effects of naps are very limited. We report on associations between napping and metabolic syndrome risk in a large older Chinese group.Methods: Data from 16 480 older participants (≥50 years) from the Guangzhou Biobank Cohort Study were analysed. Sociodemographic parameters, including frequency of lunch-time napping were coll...

One of the proposed mechanisms responsible for Diabetes mellitus (DM)-associated erectile (ED) dysfunction is overactivity of RhoA/ROCK signalling. Because statins may decrease RhoA activation, we investigated whether atorvastatin ameliorated DM-induced ED in alloxan-treated (100 mg/kg) rabbits (in vitro studies) and streptozotocin-treated (STZ, 50 mg/kg) rats (in vivo studies). A subgroup of diabetic animals received atorvastatin 5 mg/kg per daily 2 weeks before...

Gsα is a ubiquitously expressed G protein α-subunit that couples receptors to adenylyl cyclase and cAMP generation. In patients with Albright hereditary osteodystrophy (AHO), heterozygous Gsα mutations only lead to obesity when present on the maternal allele. Similarly, mice with heterozygous germline Gsα mutations on the maternal allele develop severe obesity and insulin resistance with reduced energy expenditure relative t...

Bile acids (BAs) are potent signaling molecules that regulate glucose, lipid and energy homeostasis predominantly via farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor 5 (TGR5). Modulation of bile acid profiles might affect the treatment of metabolic diseases, indicating new possible therapeutic avenues. The sodium taurocholate co-transporting polypeptide (NTCP) plays a pivotal role in the enterohepatic circulation of bile salts as the main uptake transpo...

Introduction: Transcriptional regulation of gene expression by miRNAs is critical for the fine-tuning of adrenal stress response. However, its role in hypercortisolism has not been explored well. The study addresses this gap using adrenal samples of 3 patient groups from the German Cushing’s registry: Cortisol-Producing-Adenoma (CPA), Primary Bilateral Adrenal Hyperplasia (PBMAH) and controls (adrenal samples of patients with pheochromocytoma).Metho...

Background: Small intestinal neuroendocrine tumor (SI-NET) is one of the major cancer subtypes of the small bowel. Most SI-NETs locate in the terminal ileum with a high incidence of multiple synchronous primary tumors. The only essentially curative treatment of SI-NETs is complete surgical resection; however, most SI-NET patients cannot undergo surgery as they typically present with an extensive metastatic disease. Several high-throughput sequencing studies have reported low s...