title: Effects of glucocorticoids and sympathomimetic agents on basal and insulin-stimulated glucose metabolism.
abstract: The mechanisms responsible for glucocorticoid-induced insulin resistance remain unclear. Glucocorticoids show several interactions with the sympatho-adrenal system which may contribute to this decrease in insulin sensitivity: they enhance the synthesis and actions of catecholamines, but abolish insulin-induced activation of muscle sympathetic nerve activity. The present study was performed in order to investigate the effects of the interactions between glucocorticoids and the sympatho-adrenal system on insulin sensitivity. Basal and insulin-stimulated glucose metabolism was measured in healthy human subjects during four 2-h clamp studies as follows: control (C); after taking oral dexamethasone (2 mg daily) for 2 days (D); after taking oral ephedrine sulphate (40 mg daily) for 2 days (E); and after taking dexamethasone+ephedrine (D+E). Glucose uptake, production and oxidation were calculated from plasma 13C glucose and exhaled 13CO2 during constant tracer infusion of U-13C glucose. Basal glucose production, utilization and oxidation were similar in all four studies. During hyperinsulinaemia, glucose uptake was reduced by 51.5% with treatment D, by 25.9% with treatment E, and by 49.6% with D+E. Glucose oxidation was reduced by 54.0% with treatment D, by 24.0% with treatment E, and by 57.2% with D+E. Hepatic glucose production was completely suppressed in all four studies. It is concluded that both dexamethasone and ephedrine decrease insulin-mediated glucose uptake and oxidation. Co-administration of ephedrine does not suppress the glucocorticoid-induced alterations of glucose metabolism. This indicates that glucocorticoid-induced insulin resistance is not related to the inhibition of muscle sympathetic nerve activity. These results suggest instead that glucocorticoids and sympathomimetic agents may impair glucose metabolism by common actions.
authors.affiliation: Institute of Physiology, Faculty of Medicine, Lausanne University, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Paquot
authors.forename: P
authors.initials: P
authors.lastname: Schneiter
authors.forename: E
authors.initials: E
authors.lastname: Jéquier
authors.forename: L
authors.initials: L
authors.lastname: Tappy
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D004809:Ephedrine / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D010084:Oxidation-Reduction; D013268:Stimulation, Chemical; D013566:Sympathomimetics / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D005938:Glucocorticoids; D007328:Insulin; D013566:Sympathomimetics; D003907:Dexamethasone; D004809:Ephedrine; D005947:Glucose