Effects of dexamethasone on the metabolic responses to mental stress in humans

Abstract

The haemodynamic effects of the sympathetic nervous system (SNS) activations elicited by hypoglycaemia, acute alcohol administration, or insulin can be prevented by a pretreatment with dexamethasone in humans. This suggests a possible role of central corticotropin releasing hormone (GRIT) release. Mental stress activates the SNS, and decreases systemic vascular resistances though a beta-adrenergic-mediated vasodilation thought to involve vascular nitric oxide release. It also increases insulin-mediated glucose disposal, an effect presumably related to vasodilation. In order to evaluate whether activation of SNS by mental stress is glucocorticoid-sensitive, we monitored the haemodynamic and metabolic effects of mental stress during hyperinsulinaemia in healthy humans with and without a 2-day treatment with 8 mg day(-1) dexamethasone. Mental stress decreased systemic vascular resistances by 21.9% and increased insulin-mediated glucose disposal by 2 8.4% without dexamethasone pretreatment. After 2 days of dexamethasone treatment, whole body insulin-mediated glucose disposal was decreased by 40.8%. The haemodynainic effects of mental stress were however, not affected. Mental stress acutely increased insulin-mediated glucose disposal by 28.0%. This indicates that mental stress elicits a stimulation of SNS through dexamethasone-insensitive pathway, distinct of those activated by insulin, alcohol, or hyperglycaemia.

Exercise

“…Although hypoglycemia is not an issue in the management of ADHD, some of the above concepts may be relevant to ADHD children, as the underlying mechanism triggered during hypoglycemia, such as activation of the hypothalamic–pituitary–adrenal axis (i.e., Volkow et al, 2011), is shared by other stimuli. It has in fact been clearly documented that a prior intense emotional experience (Seematter, Battilana, & Tappy, 2002), or a prior intense exercise challenge (Sandoval, Guy, Richardson, Ertl, & Davis, 2004), also result in significant blunting of catecholamine and other physiological responses to a stress occurring during the following hours to days. This “interchangeability” of the prior blunting stimulus may suggest that yet other factors may be at play (especially emotional/psychological elements), possibly further modulating the presence and the magnitude of alterations in catecholamine secretion in ADHD and other children, in basal conditions or in response to specific triggers.…”

Facultative adjustment of mammalian sex ratios in support of the Trivers–Willard hypothesis: evidence for a mechanism

“…Lond. B (2004) prevented by the administration of dexamethasone (Pratt & Lisk 1990), which, among other actions, inhibits glucose transport and lowers plasma glucose (Hahn et al 1999;Shamey et al 2000;Buren et al 2002;Seematter et al 2002), without a major impact on follicular development. (ii) A study using mice as an animal model for human diabetes found that an increase in circulating glucose resulted in a male-biased sex ratio (Machado et al 2001).…”

Stress and Metabolism

“…27,28 The sympathetic stimulation elicited by mental stress appears to differ from other procedures in this respect, as it is not inhibited by dexamethasone in healthy humans. 29 This suggests that the central pathways involved during mental stress differ from other sympathetic stimuli.…”