Endocrine Abstracts

Background: Since it has been shown that markers of oxidative stress persist in endothelial cells that have been exposed for a prolonged time to chronic constant high glucose levels, long after glucose normalization, a phenomenon defined as ‘metabolic memory’, evaluation of chronic exposure to oscillating high glucose, its impact on the induction of cellular stress markers and the onset of a ‘metabolic memory’ might be of pivotal interest. In doing so we al...

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...

Central obesity is strongly associated with insulin resistance and chronic sub-clinical inflammation, which is implicated in the development of type 2 diabetes (T2DM). However, the mechanisms underlying this link remain unclear. Recently JNK, a mitogen activated protein kinase (MAPK), has been implicated in obesity and insulin resistance by interfering with insulin action. Studies in rodent models show that phosphorylated JNK-1 is elevated in obesity, whilst the absence of JNK...

The renin-angiotensin system (RAS)is important for the regulation of blood pressure with its blockade shown to reduce the vascular complications of diabetes. Adipose tissue expresses the RAS system and may contribute to obesity associated hypertension. Our previous in vitro studies have demonstrated that in human adipose tissue production of both angiotensinogen (AGT) and the active metabolite angiotensin II are stimulated by insulin. The present study investigated the ...

Introduction: Denosumab is a human monoclonal antibody against the receptor activator of nuclear factor-kB ligand, to reduce bone resorption by limiting maturation of osteoclasts. It has been approved for use in Scotland in patients with a bone mineral density (BMD) T-score of between −4 to 2.5 who are unable to take bisphosphonates. We aimed to analyze the effects of denosumab on BMD and fracture rate in a cohort of patients who have completed a 3-year cycle of...

Introduction: Denosumab is a human monoclonal antibody against the receptor activator of nuclear factor-kB ligand, to reduce bone resorption by limiting maturation of osteoclasts. It has been approved for use in Scotland in patients with a bone mineral density (BMD) T-score of between −4 to 2.5 who are unable to take bisphosphonates. We aimed to analyze the effects of denosumab on BMD and fracture rate in a cohort of patients who have completed a 3-year cycle of...

Objective: Incidentally discovered adrenal masses (‘incidentalomas’) are found in 2% of the population. Adrenalectomy is necessary only in a small proportion of such subjects as outlined by the relevant ESE/ENSAT guideline1. However, uncertainty exists over the need for removal of lesions between 4 and 6 cm and those with low lipid content on CT scanning (found in 20% of benign adenomas). Our centre tends to offer surgery for all adenomas >4 cm.<p ...

Background/objectives: Fibroblast growth factor 21 (FGF21) is a potent hormone known to reduce glycaemia and improve insulin resistance with anti-obesity effects. Although mainly secreted in the liver, adipose tissue is considered an important target for its function. Whilst FGF21 has been shown to be expressed in murine adipose tissue, studies in human adipose tissue are lacking. Therefore our aim was to examine the expression of FGF21, FGF21 receptor-1 (FGFR1), βKlotho ...

Background: Adipose tissue (AT) plays a central role in obesity-related complications such as cardiovascular diseases, insulin resistance, and type two diabetes. A comprehensive understanding of the molecular mechanisms underlying adipocyte formation is of both fundamental and clinical relevance. It has been reported that UPR pathway, IRE1α-XBP1 regulates hepatic lipogenesis and the role of this pathway in adipogenesis in murine adipocytes has also been confirmed. Our tea...

Mitochondria are essential for synthesising ATP required for cellular metabolism. Mitochondria are able to alter their morphology and abundance through the balance of fission and fusion genes. T2DM is often accompanied by a metabolic syndrome within the individual. The aim of my PhD is to investigate whether metabolic dysregulation in T2DM can be linked to dysfunction within their mitochondria.Declaration of funding: EPSRC....