25A systems level coordination of physiological rhythms is essential to sustain healthy states, especially in 26 the face of stimuli that may disrupt such rhythms. The timing of meals, medication and chronic stress 27 can profoundly influence metabolism, which depends on the dynamic interactions between glucose, 28 insulin and cortisol. Although the metabolic and stress endocrine axes are simultaneously disrupted in 29 many diseases, a theoretical framework to understand how chronodisruption leads to disease is lacking. 30 By developing a mathematical model of glucose utilisation that accounts for the antagonism between 31 insulin and cortisol, we investigate the dynamic effects of glucose boluses under normal and disrupted 32 cortisol rhythms, including the effects of cortisol agonists and antagonists. We also predict how cortisol 33 rhythms modulate circadian responses to oral glucose diagnostic tests, and analyse the disruptions 34 caused by hypercortisolism. Finally, we predict the mechanisms leading to type 2 diabetes in patients 35 with normal and excess cortisol. 36 37 38 39 40 41 42 43 157
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.