Endocrine Abstracts

AMP-activated protein kinase (AMPK) is the downstream component of a protein kinase cascade that has been proposed to act as an important regulator of both cellular and organismal energy homeostasis. Increases in the cellular AMP: ATP ratio promotes phosphorylation and activation of AMPK by the upstream kinase LKB1. AMPK subsequently phosphorylates target proteins that inhibit ATP-consuming anabolic pathways and stimulates ATP-producing catabolic pathways. AMPK is therefore ac...

There is a significant body of research that demonstrates an association between central (visceral) obesity, insulin resistance, endothelial dysfunction and accelerated atherosclerosis, but the molecular mechanisms underlying this link are incompletely understood. In cultured human aortic endothelial cell (HAEC) models, insulin stimulates an intracellular signalling cascade resulting in activating phosphorylation of Insulin Receptor Substrate-1, Protein kinase B (PKB/Akt) and ...

Insulin resistance states are associated with endothelial dysfunction, but the molecular mechanisms underlying this association are incompletely understood. Impairment of insulin stimulated endothelial NO production is proposed to be a key mechanism in this process. In cultured human aortic endothelial cell (HAEC) models, insulin stimulates an intracellular signalling cascade resulting in activating phosphorylation of Insulin Receptor Substrate-1 (IRS-1), Protein kinase B (PKB...

Aims: Recent evidence suggests that Growth Hormone Deficiency (GHD) may be associated with cognitive impairment in adults. These findings are supported by neurobiological studies documenting the presence of GH receptors in many regions of the brain, including the hippocampus and the prefrontal cortex. However to date no comprehensive investigation of the cognitive sequelae of growth hormone deficiency in children has been undertaken. We aimed to determine the effect of GHD on ...

The PROactive study recently demonstrated that pioglitazone, a thiazolidinedione class drug, reduces macrovascular morbidity and mortality in patients with type 2 diabetes. This class of drug has been reported to exert PPAR gamma receptor dependent as well as receptor independent effects, possibly via AMP kinase activation (AMPK) but the precise mode of action resulting in improved cardiovascular outcome remains uncertain.We studied the effects of rosigl...

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...

Introduction: Following a National training programme for Endocrinologists to provide RAI treatment for benign thyroid disease, the ESHT NHS Trust started Radioactive iodine (RAI) treatment for benign thyroid disease a couple of years ago. Previously ESHT trust patients were referred to neighbouring trusts for RAI treatment.Data/Results: The data was collected over a 12-18 month period. A total of 34 patients received RAI treatment during this period; 28...

Adipose tissue inflammation may be an important mechanism in the development of systemic insulin resistance, such that modulation of this system may be a therapeutic target for type 2 diabetes and obesity-related disorders. AMPK has anti-inflammatory properties, yet the anti-inflammatory actions of AMPK in adipocytes remain poorly characterised. We questioned whether AMPK activation influences pro-inflammatory responses in cultured adipocytes in basal and stimulated conditions...

The increasing global prevalence of obesity requires urgent intervention to limit the anticipated surge of associated cardiometabolic morbidity and mortality. The energy sensor AMP-activated protein kinase (AMPK) is one proposed target for treating metabolic disorders and is downregulated in adipose tissue of obese insulin resistant individuals. Given the strong relationship between metabolic syndrome and overactivity of the renin-angiotensin-aldosterone system (RAAS) we inves...

Introduction: A previous case-report described one individual whose significant sleep disturbance in association with septo-optic dysplasia (SOD) was corrected with melatonin administration. Subsequently a trial of melatonin treatment in children with SOD and sleep disruption has become accepted clinical practice in many centres. There are however no published data describing melatonin secretion in these individuals.Methods: We studied six children with ...