Please use this identifier to cite or link to this item:
Title: Cortisol response to individualised graded insulin infusions: A reproducible biomarker for CNS compounds inhibiting HPA activation
Authors: Chen, C.L.H.
Willis, B.A.
Mooney, L.
Ong, G.K.
Lim, C.N.
Lowe, S.L. 
Tauscher-Wisniewski, S.
Cutler Jr, G.B.
Wiss, S.D.
Keywords: Cortisol
Hypothalamic-pituitary-adrenocortical axis
Insulin infusion
Insulin tolerance test
Issue Date: Dec-2010
Citation: Chen, C.L.H., Willis, B.A., Mooney, L., Ong, G.K., Lim, C.N., Lowe, S.L., Tauscher-Wisniewski, S., Cutler Jr, G.B., Wiss, S.D. (2010-12). Cortisol response to individualised graded insulin infusions: A reproducible biomarker for CNS compounds inhibiting HPA activation. British Journal of Clinical Pharmacology 70 (6) : 886-894. ScholarBank@NUS Repository.
Abstract: AIM: To determine the potential of cortisol secretion, in response to a physiological stressor, as a biomarker for centrally active compounds targeting the hypothalamic-pituitary-adrenocortical (HPA) axis. METHODS: Cortisol response to hypoglycaemia was measured in 26 healthy males in two stages: firstly to derive an algorithm for individualized, graded insulin infusion rates to achieve defined hypoglycaemic targets over 3 h and secondly to determine the inter- and intra-subject variability of cortisol response to hypoglycaemia over two identical periods by measuring the maximum (tmax), time to maximum (Cmax) response and cortisol area under the response curve (AUC). RESULTS: Hypoglycaemia induced a consistent cortisol response starting at approximately 1 h, corresponding to blood glucose concentrations of approximately 3.3 mmol l-1, and peaking approximately 3 h after the start of infusion. The inter- and intra-subject coefficients of variation (CVs) of cortisol response were approximately 19 and 19% (AUC), 15 and 19 % (Cmax) and 10 and 14% (tmax), respectively. The intra-subject CVs for the ratio of maximum cortisol response to baseline concentration and rate of initial cortisol response between study days were more variable (32.8% and 59.0%, respectively). The blood glucose-cortisol response model derived from the study was predictive of the individual observed cortisol responses, and estimated a blood glucose EC50 associated with onset of the cortisol response of 3.3 mmol l-1. CONCLUSIONS: Gradual hypoglycaemia is an effective, reproducible and well-tolerated method of stimulating a cortisol response and may therefore be useful in assessing the neuroendocrine response to HPA axis inhibitors, such as corticotropin-releasing hormone-1 (CRH-1) antagonists. © 2010 The Authors. British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.
Source Title: British Journal of Clinical Pharmacology
ISSN: 03065251
DOI: 10.1111/j.1365-2125.2010.03781.x
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.


checked on Dec 13, 2018


checked on Nov 27, 2018

Page view(s)

checked on Dec 14, 2018

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.