Endocrine Abstracts

Pancreatic islet cell transplantation is proven to restore functional beta cell mass to achieve normoglycemia in diabetics, but is limited by low availability of human cadaveric donor tissue. A strategy to build capacity is to use stem cells (SCs), and induce their expansion and differentiation into functional islets in vitro. Islet cell neogenesis has been linked to transient and sequential expression of specific transcription factors (TFs) and the actions of endogenou...

Objective: The extracellular calcium-sensing receptor (CaR) is expressed on many different cell types other than those involved in the systemic regulation of plasma calcium. We have demonstrated previously that insulin-producing beta cells express the CaR. In this study we have used a calcimimetic CaR agonist (A568) to investigate the effects of CaR activation on beta cell function.Methods: Experiments used the insulin secreting MIN6 cell line or isolate...

IntroductionThe IGF-system has also been implicated in the pathogenesis of diabetes and cardiovascular disease. We report the effects of total energy intake on the IGF-system in two populations with a markedly different dietary macronutrient intake and cardiovascular event rate.MethodDietary macronutrient intake was measured in a specific Gujarati migrant community in Sandwell UK (n=205) compared with people ...

Pro-opiomelanocortin (POMC) deficiency in mice and humans results in a syndrome of severe obesity, hyperphagia and adrenal insufficiency. We have used mice heterozygous for a null mutation in the Pomc allele (Pomc+/-) to determine if POMC haploinsufficiency results in disordered energy homeostasis or adrenal hypofunction.When fed standard lab diet (SLD, 4.5% fat) Pomc+/-were similar in weight to wild type (WT) mice thr...

Ghrelin, a circulating gastric hormone, stimulates food intake in rodents and humans and hyperphagia, weight gain and adiposity on chronic administration in rodents. Here we investigated the effect of chronic subcutaneous ghrelin on fat volume and distribution using magnetic resonance imaging (MRI). Male Wistar rats were implanted with subcutaneous osmotic mini-pumps delivering saline (S, n=10) or ghrelin 30nmol/24hours (n=18). In order to investigate the hyperphagia-independe...

Glucocorticoid metabolism is altered in a tissue-specific manner in obesity. Increased reactivation of glucocorticoids by 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1) amplifies glucocorticoid action in abdominal fat, whereas increased metabolism of glucocorticoids by hepatic A-ring reductases may contribute to activation of the hypothalamic-pituitary-adrenal axis. These changes have been characterised in leptin-resistant obese Zucker rats and obese humans. Here we inves...

Chronic sub-clinical inflammation is associated with both type 2 diabetes and related vascular complications which is coupled with pro-inflammatory markers, such as IL-6, TNF-alpha and C-reactive protein (CRP). Resistin is the latest protein to be linked with inflammation and insulin resistance in obesity. Adipose tissue has been previously established as a source of circulating resistin, TNF-alpha and IL-6. As our previous studies demonstrated a correlation between serum resi...

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) has been implicated in the pathogenesis of human obesity and insulin resistance through 11-oxoreductase activation of cortisol (F) from cortisone (E) stimulating adipocyte differentiation and hepatic glucose output. In its purified state however, 11beta-HSD1 is a dehydrogenase inactivating F to E. In patients with cortisone reductase deficiency we recently identified two inactivating mutations, delta29bp and R453Q, withi...