Endocrine Abstracts

Introduction: Insulin sensitising agents are reported to have a diverse range of effects on bone with metformin exerting positive effects and thiazolidinenediones (TZDs) exerting negative effects. 5′AMP-activated protein kinase (AMPK) plays a critical role in cellular energy homeostasis. It is widely expressed in the body and can be activated by metformin.Aim: We investigated the role of AMPK pathway in mediating the effects of metformin on the ost...

GnRH acts via Gq/11-coupled GPCRs on gonadotropes to control synthesis and secretion of LH and FSH. We use mathematical and statistical approaches as well as automated cell imaging to explore this system. In cells expressing ERK2–GFP and GnRH receptors, GnRH pulses cause rapid and transient nuclear translocation of ERK2–GFP, providing a live-cell readout for ERK activation1. A mathematical model trained against this data predicted greater sensitivity to re...

Background: 5-hydroxyindole acetic acid (5-HIAA) (a metabolite of serotonin) is used as a marker for patients with serotonin-secreting neuroendocrine tumours. Currently, most laboratories measure 24 h 5-HIAA excretion in urine samples. Urine collections are cumbersome for the patient and impact on their daily activities; they are consequently often poorly performed, leading to over- or under-collection of urine and inaccurate 5-HIAA excretion results. Furthermore, large volume...

Introduction: Hyponatraemia is the most common electrolyte disorder in hospitalised patients and is associated with significant morbidity and mortality.Methods: This retrospective study included all inpatients with serum sodium (sNa) ≤128 mmol/l at any point during hospitalisation at a teaching hospital over a 3-month period (1st March 2013 to 31st May 2013). Demographic, clinical and laboratory data obtained from patients’ case notes and labo...

Gonadotrophs in rats, mice and humans, express an intact natriuretic peptide system, in which C-type natriuretic peptide (CNP) is the predominant member. Despite showing an interaction between CNP and GnRH at the level of cGMP and Ca2+ signalling, the role of CNP in gonadotroph biology is poorly understood. In this study, we utilise a novel multiplex qRT-PCR assay, examining simultaneous expression of natriuretic peptide genes along with genes for gonadotroph transc...

Introduction: Diabetes is associated with increased fracture risk both in patients with type 1 (T1D) and type 2 diabetes (T2D) despite differences in bone mineral density BMD (decreased in T1D and increased in T2D). In T2D, insulin resistance (IR) is selective, with some insulin signaling pathways impaired, while others are overactive due to hyperinsulinemia. It is not clear how different insulin signaling pathways might contribute to the bone phenotypes observed in diabetes. ...

Background: Glucocorticoids are frequently used to treat childhood inflammatory disorders, and may cause increased fracture predisposition with reduced bone mineral density (BMD), particularly from trabecular bone loss. The contribution of the underlying inflammatory disease processes to these outcomes is poorly understood. Childhood nephrotic syndrome (NS) is a useful model to investigate the effects of steroids on bone, as recurrent courses are often required, but systemic i...

Background: Poorly controlled diabetes is associated with dyslipidaemia including high cholesterol and LDL concentrations. This increases the long term risk of atherosclerosis and cardiovascular complications. In children and young people with type 1 diabetes, management with lipid lowering agents is controversial and to date long term evidence of benefit is limited. We report a case of severe dyslipidaemia and the impact of improvement in glycaemic control.<p class="abste...

Background: Unrecognised type I diabetes (TIDM) can have serious consequences which may be avoidable with early diagnosis. Many children have delayed diagnosis, however contributing factors are unclear.Aims: To evaluate the patient pathway before diagnosis and initial hospital management of children with TIDM.Methods: Over a 3-month period, parents of children newly diagnosed with TIDM across the UK completed a questionnaire. Addit...

Tissue cortisol levels are amplified by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). In mice, transgenic overexpression of 11β-HSD1 causes the metabolic syndrome, consequently 11β-HSD1 inhibitors are a promising therapeutic target. However, determining the importance of 11β-HSD1 in humans has proved more complicated, in part due to difficulty quantifying in vivo activity. We hypothesized that cortisol regeneration by 11β-H...