Endocrine Abstracts

We have previously described a series of patients who presented with clinical and biochemical features diagnostic of phaeochromocytoma but in whom catecholamine excess proved to be secondary to undiagnosed obstructive sleep apnoea (OSA). We describe here a prospective study of 30 patients presenting to the sleep clinic with OSA from whom 24 hour urine collections were analysed for catecholamines before and after treatment with continuous positive airways pressure (CPAP).<p...

Type 2 diabetes mellitus is associated with increased incidence of low serum testosterone levels in men. Testosterone is known to be positively correlated with insulin sensitivity. Rosiglitazone is an insulin sensitizing agent that reduces insulin resistance by binding to PPAR gamma receptor. The purpose of this study was to determine the effect of Rosiglitazone on testosterone levels in hypogonadal men with Type 2 diabetes.This study was approved by BDG...

IntroductionInsulin-like growth factors-I (IGF-I) and -II (IGF-II) are important in regulation of metabolism and growth. We previously reported in normal weight normoglycaemic individuals that low circulating IGF-II predicts future weight gain. We subsequently investigated whether such relationships persisted in circumstances of abnormal glucose tolerance.MethodIn 224 type 2 diabetes subjects we assessed the ...

In previous work we demonstrated that various adipokines, including leptin and resistin, were expressed in the hypothalamus and anterior pituitary gland. We hypothesized that a practical approach to investigate the putative central role of such factors would be to selectively silence gene expression by RNA interference (RNAi). We tested this hypothesis using model in vitro systems : C6 glioblastoma cells , which we reported express leptin, and 3T3-L1 adipocytes which are known...

Aims and Methods:Obesity treatment is often unsuccessful despite the efforts of seemingly motivated patients. Awareness among the obese, regarding obesity, is important to facilitate weight loss and to prevent weight gain. We assessed the awareness of obese patients with regard to obesity, its complications and treatment options. Consecutive subjects attending outpatient clinics with BMI>/=30and <70years of age were interviewed.<p class="abstex...

Recently the American Diabetes Association (ADA) adopted a lower cut off for (IFG) Impaired fasting glucose (greater than or equal to 5.6 millimol per litre). We suggested that performing oral glucose tolerance tests (OGTT), in all subjects with IFG according to the new ADA criteria, would result in very little new diagnosis of Diabetes Mellitus (DM) and to test this hypothesis we reviewed our recent experience with OGTTs.Between August 2001 and June 200...

We aimed to establish the extent of adult cystic fibrosis-related diabetes (CFRD) in Ireland, and examine the differences between patients with CFRD and those with normal glucose handling.We conducted a retrospective analysis of patients with cystic fibrosis (CF) who attend the national referral centre for adult CF. Data including lung spirometry, sputum microbiology, bone mineral density and genotype were collected. Patients were diagnosed as having CFR...

Type 2 diabetes mellitus (T2DM) is associated with insulin resistance/ hyperinsulinaemia and chronic sub-clinical inflammation that is considered important in the pathogenesis of macrovascular disease. We propose activation of the innate immune system, a biologically conserved first line immune response, within adipose tissue by endotoxaemia secondary to hyperinsulinaemia as one of the causes of this phenomenon. Hyperinsulinaemia may lead to altered gut permeability and result...

Objective: To study serum levels of angiogenic factors: vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiogenin and transforming growth factor-beta 1 (TGF-beta 1) and their relationship to metabolic control in children and adolescents with type 1 diabetes mellitus and to evaluate whether these angiogenic factors can predict and identify cases at greater risk to develop diabetic retinopathy or persistent microalbuminuria in a follow-up perio...

Objective: to study nerve functions in IDDM at an early stage to evaluate the prevalence of neuropathy.Subjects and methods: The study included 20 children with IDDM and 10 healthy subjects as controls. Patients were subjected to clinical evaluation of neuropathic manifestations. Laboratory tests included fasting blood glucose and serum glycated hemoglobin (HbA1c). Electrophysiological study included motor conduction studies of the median and deep perone...

Type 2 diabetes (T2DM) is associated with a 2-4 fold increased risk of mortality largely due to cardiovascular disease.Therefore patients with newly diagnosed (T2DM) are at increased cardiovascular risk and may already have cardiovascular complications. Estimating the risk of future events would be important towards potential preventative measures. Ethics Committee Approval was obtained to estimate the risk of vascular complications in a cohort of newly ...

The vasodilator minoxidil is a potent antihypertensive agent. However, its use has been rather limited and it can easily be overlooked in the era of ACE inhibition and angiotensin receptor blockade. It must be used with diuretic and beta-blocker cover.We reviewed 13 male patients with refractory hypertension attending our hypertension clinic from January to July 2004 and currently receiving minoxidil. Analysis was with paired t-tests.<p class="abstex...

AimsTo compare baseline demographical and anthropometrical characteristics of patients referred to the multi-disciplinary weight management clinic at University Hospital Nottingham during 2003 with patients referred in 2001, co- morbidities, treatments used and achievement of the desired outcome of realization of 5 or 10 percent weight loss sustained over a 6-month period of follow-up.Results and DiscussionWe...

We have investigated the effects of estradiol valerat plus dienogest and raloxifene on serum high sensitive C - reactive protein (hsCRP) levels in healthy postmenopausal women. This study was approved by the local ethics committee. Forty eight healthy postmenopausal women were randomly divided into three groups. While group I (n=16) was given 60 mg raloxifene, group II (n=16) received continuously 2 mg estradiol valerat plus 2 mg dienogest. Group III (n=16) received no medicat...

Prostanoids have been elucidated as potent adipogenic hormones. Cyclooxygenase (PTGS) is the rate-limiting enzyme of prostanoid biosynthesis and its product, prostaglandin (PG) H2 is a precursor of PGE2, PGF2, PGD2 and PGI2. PGH2 is also metabolised by prostaglandin D-synthase (PTGDS) to PGD2 which spontaneously converts to PGJ2 or can be enzymatically converted to PGF2alpha by AKR1C3. These two metabolites have opposite effect on adipogenesis; PGF2alpha is a PPARgamma antagon...

Neuronal glucose and insulin signals are integrated by hypothalamic neurons to regulate energy balance. These signalling mechanisms are not clearly defined in the hypothalamus, and may be altered in obesity and diabetes. This study aimed to analyse quantitatively hypothalamic expression of candidate genes in signal transduction pathways and investigate dysregulation using Zucker and Zucker Diabetic Fatty (ZDF) models.Taqman RT-PCR was used to compare exp...

Glucocorticoid excess results in central obesity and insulin resistance/diabetes mellitus. At a pre-receptor level, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) modulates glucocorticoid levels and has been implicated in the pathogenesis of the metabolic syndrome. 11beta-HSD1 is a bi-directional NADP(H) dependant enzyme, but keto-reductase activity predominates in-vivo. Recent studies indicate that the enzyme H6PDH ensures reductive metabolism (cortisone to c...

In humans, glucocorticoids (GC) are implicated in the pathogenesis of obesity and insulin resistance. GCs are regulated at the prereceptor level by 11beta-HSDs. 11beta-HSD1 predominately displays oxo-reductase activity (cortisone/11-dehydrocorticosterone to cortisol/ corticosterone), requiring the cofactor NADPH. Recently, studies in humans have shown that the enzyme H6PDH, by generating NAPDH in the endoplasmic reticulum (ER) is crucial for oxo-reductase activity. This study ...

Introduction: Low endogenous testosterone is associated with atherosclerosis in elderly men. The aim of this study was to determine whether an inactive androgen receptor (AR) coupled with testosterone deficiency, inherent to the testicular feminised (Tfm) mouse, is associated with atherosclerosis following cholesterol feeding.Methods: Eight-week-old Tfm (n=34) and XY (n=32) littermate controls were fed for 16, 20, 24 or 28 weeks on either diet 1 (compris...

Ghrelin is an orexigenic hormone, the endogenous ligand of the previously orphan growth-hormone-secretagogue receptor (GHS-R). Recently, it has been reported that pancreatic beta-cells are replaced by ghrelin-producing cells in a diabetic mice model implicating these genes as attractive candidates in the aetiology of type 2 diabetes (T2D) (PNAS;101:2924). The ghrelin gene is located at 3p25-26 and its cognate receptor at 3q26. We aimed to test for an association of these two g...

Obesity-mediated diabetes is associated with insulin resistance/hyperinsulinaemia and chronic sub-clinical inflammation. Recent studies have highlighted fatty liver(steatosis) as a risk factor for diabetes. Fatty liver disease (FLD) progresses through fatty liver, necro-inflammation (non-alcoholic steatohepatitis, NASH) and fatwith fibrosis. In addition, hepatic steatosis per se can lead to hepatic insulin resistance/hyperin...

Epidemiological studies have suggested that in man low birth weight followed by rapid catch-up growth dramatically increase the risk of adulthood diabetes and metabolic syndrome. This experiment investigated the effect of a high fat, high cholesterol post-weaning diet on blood glucose levels of low (L) and normal (N) birth weight pigs.Low (L: <10thpercentile; n=6) and normal (N: 40th - 60th percentile; n=12) birth weig...

PCOS is associated with insulin resistance and dyslipidaemia. Adiponectin receptors (Adipo-R1, Adipo-R2) are expressed in human myotubes. Their mRNA levels were found to be correlated with insulin and circulating triglycerides.The aims of this study, were to investigate the expression of adiponectin and its receptors in adipose tissue from normal and PCOS women (Ethical approval was obtained from the University Hospitals Coventry & Warwickshire NHS T...

Vascular calcification is a regulated process with similarities to osteogenesis, however, the precise mechanism underlying this process is poorly understood. Pericytes are pluripotential microvascular cells which have been shown to differentiate along an osteogenic lineage. Glucocorticoids are widely prescribed drugs but have adverse side-effects including both vascular lesion formation and bone loss. The mechanism underpinning the contrasting effects of dexamethasone (dex) on...

Lys-gamma3-MSH is a peptide derived from the multihormone precursor protein pro-opiomelanocortin (POMC). Lys-gamma3-MSH increases cholesterol ester hydrolysis and mitochondrial cholesterol accumulation in the adrenal gland by activating the enzyme cholesterol ester hydrolase (CEH). Although the receptor through which the actions of Lys-gamma3-MSH on the adrenal gland are mediated remains to be identified, ligand binding studies suggest the existence of binding sites in adipose...

Testosterone is a coronary vasodilator and is known to increase ischaemic threshold in men with angina. We have previously demonstrated that testosterone inhibits the pore forming alpha1c subunit of the cardiovascular L-type calcium channel transfected into HEK293 cells. In this study we have investigated the effect of testosterone on potassium-stimulated extracellular calcium entry in A7r5 vascular smooth muscle cells (VSMCs).A7r5 cells grown...

There is evidence that an unbalanced maternal diet, combining a high ratio of protein to carbohydrate with low intakes of folate and green vegetables imposes a metabolic stress on the mother and fetus leading to fetal growth retardation. Because recent studies have shown that high protein maternal diets are associated with raised offspring blood pressure, we have assessed whether this form of unbalanced maternal nutrition is also associated with glucose intolerance.<p clas...

The adrenal gland is implicated in energy homeostasis, and dysfunction of this gland contributes to a variety of metabolic disorders including the development of hypertension, diabetes, osteoporosis, and obesity. Recently, adipokines have been implicated in adrenal function. Adiponectin, an adipokine, with insulin sensitising and anti-inflammatory properties, exerts its effects by activating two distinct seven transmembrane domain receptors, adiponectin-R1 (adipoR1) and -R2 (a...

Diabetes mellitus, characterised primarily by hyperglycaemia, is associated with a number of cellular stresses and changes that cause cardiomyocytes to adapt with those modifications that characterise the diabetic heart. Although orexins are cardiovascular regulators acting via the brain, little is known about their potentially critical roles in the heart. Orexins exert their actions by activating two distinct G protein coupled receptors, orexin-R1 (OXR1) amd orexin-R2 (OXR2)....

Primary aldosteronism (PA) is characterized by development of cardiovascular and metabolic complications. We retrospectively analyzed 78 patients with PA: 29 had aldosterone-producing adenoma (APA), and 49 had idiopathic hyperaldosteronism (IHA). The study of complications was performed by examining the lipid and glucose profiles (OGTT, HOMA and Quicki indexes) and the echocardiographic parameters. Single-nucleotide polymorphisms (SNPs) of the aldosterone synthase (minus 344C/...

Chronic sub-clinical inflammation is associated with increased risk of type 2 diabetes and cardiovascular disease. Patients undergoing CABG are at high risk of further cardiovascular events and also demonstrate sub-clinical inflammation. We therefore investigated alterations in the relative balance between pro-inflammatory agents, such as hsCRP versus changes in anti-inflammatory factors (adiponectin) and as such the potential molecular pathways mediating these changes. The ai...

Thiazolidinediones and biguanides improve insulin resistance and are used in the management of type 2 diabetes. Use of biguanides is associated with a reduction in vascular complications in patients with diabetes. Pre-clinical studies with thiazolidinediones suggest improvements in vascular function and long-term clinical trials in type 2 diabetes are in progress. These effects are proposed to be mediated through inhibition of complex 1 in the mitochondrial respiratory chain a...

Vascular smooth muscle cells (VSMC) form a major constituent of the atherosclerotic plaque providing structural stability. However, increased cell number due to high proliferation rates can lead to greater artery occlusion. Testosterone replacement therapy improves exercise capacity and reduces symptoms of angina in men with coronary artery disease, although its effect upon VSMC growth is currently unknown. Testosterone deficiency is associated with increased atheroma burden a...

The murine ACTH receptor MC2-R is primarily expressed in the adrenal cortex and adipocytes where it binds ACTH leading to steroidogenesis and lipolysis, respectively. We have recently shown that the previously described 'adrenal' MC2-R promoter is transiently activated by PPAR gamma 2 early during differentiation of murine 3T3-L1 pre-adipocytes, declining to background levels from a peak of activity seen at day 4 following commencement of adipogenesis. This is mirrored by the ...

Several studies have demonstrated that atherosclerosis is associated with low serum levels of testosterone and replacement therapy reduces myocardial ischaemia in men. Vascular smooth muscle cell (VSMC) apoptosis reduces plaque stability. The role of testosterone if any, in this process is unknown. Testosterone has been demonstrated act via both the classic androgen receptor and by calcium channel antagonism. Calcium channel blockers have been shown to induce VSMC apoptosis. W...