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Title: Visceral adipokines, inflammation and insulin action in dysmetabolic states
Author: Tan , Bee Kang
ISNI:       0000 0004 2746 4534
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2012
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PCOS is the commonest endocrine disorder amongst women associated with insulin resistance and adverse metabolic outcomes e.g. T2DM, dyslipidemia. TlDM, another metabolic disorder, on the other hand, results from auto immune destruction of insulin- producing pancreatic ~-cells, leading to hyperglycemia and its deleterious effects. The metabolic syndrome is associated with accumulation of visceral AT, which produces cytokines termed 'adipokines' implicated in the pathogenesis of diabetes and atherosclerosis. Circulating and AT omentin-l, an insulin sensitizing adipokine, were decreased in women with PCOS; metformin treatment (6 months) increased circulating omentin-l levels. Insulin and glucose decreased omentin-l production in AT; insulin also decreased circulating omentin-l in vivo. Furthermore, in vitro migration and angiogenesis were increased by serum from PCOS women compared to controls; these effects were attenuated by metformin treatment plausibly through the regulation of omentin-l levels via NF-KB (a pro-inflammatory nuclear transcription factor) and Akt pathways. CRP and VEGF induced in vitro migration and angiogenesis was decreased by omentin-l. In another study, there was a decrease in circulating omentin-l together with an increase in circulating adiponectin (fasting and postprandial), in TlDM subjects. Also, circulating and AT ASAA, a pro-inflammatory adipokine, which antagonizes insulin action, were increased in women with PCOS; metformin treatment (6 months) decreased circulating ASAA levels. Glucose increased ASAA production in AT. ASAA production by macrophages may account for these observations. Finally, circulating HMW and total adiponectin, an anti-inflammatory and insulin sensitizing adipokine, were higher in the morning and lower at night; corresponding NF-KB activities in serum treated endothelial cells were lower in the morning and higher at night. Hyperinsulinemic induction decreased HMW and total adiponectin levels but increased NF-N B activity in serum treated endothelial cells. These studies provide novel insights into the biology of adipokines, inflammation and insulin action pertinent to dysmetabolic states such as PCOS and diabetes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available