Abstract

Clinical Untargeted Metabolomics to Study the Effects of Glucocorticoids Administration and their Interaction with Insulin

Riccardo Di Guida, PhD Student, University of Birmingham

Cortisol is an endogenous glucocorticoid that has been related with anti-inflammatory response thus leading to the widespread use of glucocorticoids in inflammatory-related and other clinical treatments. Glucocorticoids are known to regulate carbohydrate and lipid metabolism but the global metabolic effect of cortisol treatment and its interaction with other metabolic regulators (e.g. insulin) have not been fully investigated. Untargeted UPLC-MS metabolomics studies of human serum have been applied to investigate the global metabolic effects of cortisol administration and the metabolic consequence of interaction between cortisol and insulin. Here we will present results from two separate studies; (1) the metabolic perturbations of cortisol and insulin, separately and in combination in a double-blind, randomized, placebo-controlled, crossover study and (2) the metabolic effects of two 5-alpha reductase steroid metabolism inhibitors and their interaction with insulin. These studies have shown global metabolic changes, with siginificant emphasis in lipid metabolism, a possible suppression operated by insulin on the metabolic changes following cortisol administration and a negating effect on the metabolic actions of insulin by the two 5-alpha reductase inhibitors. This research opens up new advances in studying the interactions between endogenous and exogenous metabolites and metabolic-regulating hormones.