Endocrine Abstracts

Background: Poor glycaemic control with erratic blood glucose levels manifesting as recurrent hyperglycaemia with unpredictable episodes of hypoglycaemia is problem still faced today in daily practice. The causes include poor compliance and failure of oral hypoglycaemic. Despite being on insulin (38% of type 2 diabetes patients who require insulin treatment after 10 years) and type 1 diabetes patients continue to have fluctuating glucose concentration. The poor glycaemic contr...

Background/aims: Saxagliptin is a potent, selective dipeptidyl peptidase-4 (DPP-4) inhibitor, specifically designed for extended inhibition of the DPP-4 enzyme. Saxagliptin is cleared by both metabolism and renal excretion. The aims of this study were to determine the effect of renal impairment (RI) and haemodialysis (HD) on the pharmacokinetics of saxagliptin.Methods: This open-label, parallel-group study was conducted in subjects with normal renal func...

Osteosarcoma (OS) is an aggressive malignant tumour of osteoblasts occurring predominantly in children and young adults. Despite chemotherapy relapse is common and mortality remains ~50%. Non-transformed osteoblasts are highly sensitive to glucocorticoids which reduce proliferation and induce apoptosis. Previously, we observed that OS cells, but not normal osteoblasts, express 11beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2). This enzyme powerfully inactivates cortis...

Background: The hypothalamus is a critical area of the brain involved in the regulation of appetite. Cerebellin1 (Cbln1) is a highly conserved 16 amino acid neuropeptide. High levels of Cbln1 mRNA expression are found in specific hypothalamic areas involved in appetite regulation.Aim: To examine the effects of Cbln1 on food intake in rodents.Methods: 1. Ad libitum fed rats were injected intracerebroventricularly (ICV) with Cbln1 (1...

NESFATIN-1 is a recently identified hypothalamic satiety molecule derived from its precursor protein, NEFA/nucleobindin2 (NUCB2). Although the hypothalamus is considered the cornerstone for maintenance of energy homeostasis, adipose tissue plays an important role in the integration of metabolic activity and energy balance; communicating with peripheral organs and the brain via secreted proteins, termed adipokines. Many hypothalamic satiety regulatory peptides have been describ...

Carriage of the exon 3 deletion in the GH receptor (GHR) gene has been reported to enhance growth response to GH therapy in a range of conditions. JAK2 and PI3Kinase are involved in signal transduction from the GH (JAK2/PI3Kinase) and IGF-1 (PI3Kinase) receptors. We have investigated whether single nucleotide polymorphisms within these genes influence growth response to GH therapy. DNA was taken, with ethical approval, from 97 children treated with GH therapy in a single growt...

GH/IGF1 stimulate muscle function whereas excess glucocorticoids induce myopathy. Myocytes express 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an enzyme which converts inactive cortisone to active cortisol. GH/IGF-I inhibit 11β-HSD1 expression in some tissues and thus reduce cellular glucocorticoid exposure. This suggests that anabolic actions of GH/IGF1 could be mediated indirectly through effects on 11β-HSD1. The regulation of 11β-HSD1 has be...

A 69-year-old Iraqi lady presented with a 4-day history of diplopia, headache and right eye swelling. She had a pituitary adenoma diagnosed in Beirut when she was 20 years old and underwent trans-frontal surgeries and radiotherapy twice and further transsphenoidal surgery in 1980. She was on prednisolone 2 mg+1 mg and thyroxine 50 mcg daily.She initially presented to the ophthalmology clinic. Examination revealed a pupil-sparing 3rd nerve palsy of the ri...

Background: A polymorphism of the GHR gene, deletion of exon 3 (d3 GHR), has been associated with improved growth response to GH in some studies. We investigated the effect of this polymorphism across several diagnoses, evaluating parameters of growth outcome from a single institution (Manchester) and combined these with those derived from the literature using meta-analytical approaches.Methods: GHR genotype was assessed by PCR and related to clinical an...

Background/objective: We have shown that expression of maternal serum human chorionic gonadotrophin (hCG) oligossacharides in uncomplicated pregnancy differs from that seen in pregnancy complicated by maternal type1 diabetes mellitus. Whether this observed oligosaccharide heterogeneity in type1 diabetes is specific to hCG or represents a more general phenomenon amongst placental oligosaccharides is not known. The oligosaccharide distribution in placentas from pregnancies compl...