The study of the effect of glucocorticoids on global and tissue-specific metabolism in humans

[摘要] Glucocorticoids are a class of steroid hormones which are highly relevant in human health and disease as they are involved in the regulation of carbohydrate, protein and fatty acid metabolism and are instrumental in the onset or progression of various diseases including those associated with glucocorticoid deficiency or excess. As an example, cortisol and insulin are involved in diurnal metabolic processes but their effects and interaction on healthy subjects are not completely elucidated yet. My PhD programme had the objectives to (1) assess and validate computational methodologies for application in untargeted metabolomic studies of healthy humans and those diagnosed with glucocorticoid-related diseases and (2) to investigate the global and tissue-specific metabolic changes induced by glucocorticoid excess and deficiency and their integrated effects with the relevant hormone insulin. A study of data pre-processing methods applied for untargeted metabolomics including different normalisation, missing value imputation, transformation and scaling methods were investigated on an in-silica modified dataset. The results showed that different combinations of data pre-processing methods influenced the results and different data pre-processing methods should be applied for univariate and multivariate analysis. Untargeted metabolomic studies ofbiotluids were applied to investigate in-vivo global effects of glucocorticoids. The study of the separate and integrated effects of cortisol and insulin showed that insulin may have negating effects on the influence of cortisol and treatment with cortisol should be timed appropriately during the day to minimize the effect of insulin on the therapeutic effect of cortisol. The studies reported here have shown the influence of the interactions between glucocorticoids and insulin across the metabolic network.

[发布机构] University:University of Birmingham;Department:School of Biosciences

[关键词] Q Science;QH Natural history;QH301 Biology