Searchable abstracts of presentations at key conferences in endocrinology

ea0014oc9.2 | Signal transduction | ECE2007

The human orexin receptor type 2 gene: Alternative promoters determining tissue-specific expression and identification of alternate splice variants and altered translational activities

Chen Jing , Randeva Harpal

Orexins, acting via their receptors, are involved in the control of feeding, sleep-wakefulness, arousal, neuroendocrine homeostasis and autonomic regulation. However, the 5′ structure and regulation of human orexin type 2 receptor (OX2R) gene remains is not known. We present original findings regarding the 5′ structural organization of the human OX2R gene and identify four OX2R mRNA transcripts that differ in their 5′-untranslated region (UTR). The four trans...

ea0013p177 | Diabetes, metabolism and cardiovascular | SFEBES2007

The human orexin receptor type 2 gene: Alternative promoters determining tissue-specific expression and identification of alternate splice variants and altered translational activities

Chen Jing , Randeva Harpal

Orexins, acting via their receptors, are involved in the control of feeding, sleep-wakefulness, arousal, neuroendocrine homeostasis and autonomic regulation. However, the 5′ structure and regulation of human orexin type 2 receptor (OX2R) gene remains is not known. We present original findings regarding the 5′ structural organization of the human OX2R gene and identify four OX2R mRNA transcripts that differ in their 5′-untranslated region (UTR). The four trans...

ea0019p145 | Diabetes, Metabolism and Cardiovascular | SFEBES2009

Autocrine/paracrine regulation of visfatin induced MCP-1: enhanced pro-angiogeneic effects of visfatin in the human endothelium

Adya Raghu , Tan Bee , Chen Jing , Randeva Harpal

Objectives: Visfatin and monocyte-chemoattractant-protein-1 (MCP-1) are elevated in cardiovascular pathologies, insulin-resistant and dysmetabolic states. Visfatin has been reported to exhibit pro-angiogenic actions in human endothelial cells by the induction of endothelial gelatinases and VEGF. Given MCP-1’s well described pro-angiogenic properties we sought to study the potential interaction between visfatin, MCP-1 and VEGF in human endothelial cells. More importantly, ...

ea0019p314 | Steroids | SFEBES2009

The adipokine, Pre-B cell colony enhancing factor (PBEF)/visfatin, activates steroidogenic acute regulatory protein (StAR) protein expression and steroid production in human adrenocortical-H295R-cells via MAPK and PI3/AkT signalling pathways

Kaur Jaspreet , Ramanjaneya Manjunath , Chen Jing , Randeva Harpal

PBEF/Visfatin is an adipokine highly enriched in adipose tissue which is increased in obesity and has been shown to be involved in numerous physiological processes. The adrenal gland plays a pivotal role in the integration of metabolic activity and energy balance, through production of steroids, mainly glucocorticoids. Steroidogenesis is a tightly controlled and essential process, which is mediated by steroidogenic acute regulatory protein (StAR), a protein that transports cho...

ea0016oc6.1 | Metabolism and cardiovascular | ECE2008

The signaling profile of recombinant human orexin-2 receptor (OX2R)

Tang Jiyou , Chen Jing , Conner Alex , Punn Anu , Randeva Harpal

Orexin-A and orexin-B orchestrate their diverse central and peripheral effects via two G-protein coupled receptors, orexin-1 receptor (OX1R) and OX2R, which activate multiple G-proteins. In many tissues, orexins activate MAPKs, however, the mechanism by which OX2R alone mediates MAPK activation is not understood. We studied the intracellular signaling mechanisms involved in OX2R-mediated ERK1/2 and p38 MAPK activation. In HEK-293 cells stably over-expressing recombi...

ea0016oc6.3 | Metabolism and cardiovascular | ECE2008

Visfatin induces MMP-2/9 activation in human vascular endothelial cells via nuclear factor-κB

Adya Raghu , Tan Bee , Chen Jing , Randeva Harpal

Aim: Cardiovascular disease is more common in individuals with diabetes mellitus and obesity. Visfatin is elevated in obesity and T2DM; and thought to be an inflammatory mediator within atherosclerotic lesions inducing gelatinase activity, contributing to plaque destabilisation. We investigated the activation of NF-κB, a well-known pro-inflammatory transcription factor, by visfatin, in Human Endothelial Cells (EC).Research design and methods: We sta...

ea0034p263 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2014

Renalase a key regulator of brown adipose tissue activity

Ramanjaneya Manjunath , Tan Bee , Patel Vanlata , Hu Jiamiao , Lehnert Hendrik , Hillhouse Edward , Chen Jing , Randeva Harpal

Renalase is a recently discovered flavin adenine dinucleotide (FAD)-dependent oxidase, predominantly secreted into the circulation from the kidney and regulates catecholamine degradation and metabolism. Renalase gene is also present in heart muscle, skeletal muscle and liver cells in humans, and in mouse testicles. Four isoforms of renalase gene has been identified in humans (hRenalase1 to hRenalase4), however only hRenalase1 is detected in human blood suggesting that hRenalas...

ea0019oc7 | Young Endocrinologist prize session | SFEBES2009

In vivo and ex vivo regulation of Visfatin production by leptin in human and murine adipose tissue: role of the PI3K and MAPK pathways

Tan Bee , Chen Jing , Brown James , Adya Raghu , Ramanjaneya Manjunath , Bailey Cliff , Lehnert Hendrik , Randeva Harpal

Apart from its role in energy storage, adipose tissue produces several hormones and cytokines termed ‘adipokines’ that have wide-ranging effects on carbohydrate and lipid metabolism; and thereby, play an important role in the pathogenesis of the metabolic syndrome. Visfatin is a novel adipokine, levels of which increase in obesity and is adipogenic; properties common to that of leptin. Thus, leptin may modulate visfatin production in adipose tissue. We investigated t...

ea0019p131 | Diabetes, Metabolism and Cardiovascular | SFEBES2009

Identification of nesfatin-1/NUCB2 as a novel depot-specific adipokine in human and murine adipose tissue: aletered levels in obesity and food deprivation

Ramanjaneya Manjunath , Chen Jing , Brown James , Patel Suketu , Tan Bee , Randeva Harpal

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...

ea0019p146 | Diabetes, Metabolism and Cardiovascular | SFEBES2009

Metformin decreases angiogenesis via ERK1/2/ERK5 pathways by increasing the anti-angiogenic adipokine thrombospondin-1

Tan Bee , Kumar S Prashanth , Chen Jing , Heutling Dennis , Mitchell Dan , Lehnert Hendrik , Randeva Harpal

Aims: Polycystic ovary syndrome (PCOS) is associated with insulin resistance, obesity and cardiovascular complications. Thrombospondin-1 (TSP-1) is a novel anti-angiogenic adipokine highly expressed in obese, insulin-resistant subjects. We sought to assess TSP-1 levels in adipose (AT) from PCOS women and matched controls. The effects of metformin treatment on circulating TSP-1 levels in PCOS subjects; effects of serum from normal and PCOS women on in vitro migration and...