This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Perry, C. G. Articles by Connell, J. M. C. Search for Related Content PubMed PubMed Citation Articles by Perry, C. G. Articles by Connell, J. M. C.

Glucocorticoids and Insulin Sensitivity: Dissociation of Insulin’s Metabolic and Vascular Actions

University Department of Medicine, Western Infirmary (C.G.P., S.J.C., J.M.C.C.); University Department of Medicine, Royal Infirmary (G.D.O.L., J.R.P.); and Institute of Biomedical and Life Sciences, University of Glasgow (A.S.), Glasgow, Scotland, United Kingdom G11 6NT

Address all correspondence and requests for reprints to: Dr. Colin Perry, Division of Cardiovascular and Medical Sciences, Gardiner Institute, Western Infirmary, Church Street, Glasgow, United Kingdom G11 6NT. E-mail: colin{at}fulcrum.u-net.com.

Insulin sensitivity in tissues such as a skeletal muscle and fat is closely correlated with insulin action in the vasculature, but the mechanism underlying this is unclear. We investigated the effect of dexamethasone on insulin-stimulated glucose disposal and vasodilation in healthy males to test the hypothesis that a reduction in glucose disposal would be accompanied by a reduction in insulin action in the vasculature. We performed a double-blind, placebo-controlled, cross-over trial comparing insulin sensitivity (measured by the euglycemic hyperinsulinemic clamp) and vascular insulin action (measured by small vessel wire myography) in young healthy males allocated to placebo or 1 mg dexamethasone twice daily for 6 d, each in random order. Six days of dexamethasone therapy was associated with a 30% (95% confidence interval, 19.1–40.0%) fall in insulin sensitivity. Despite this, there was no difference in insulin-mediated vasodilation between phases. Dexamethasone had no effect on circulating markers of endothelial function, such as D-dimer, von Willebrand factor, and tissue plasminogen activator. By short-term exposure to high dose dexamethasone we were able to differentially affect the metabolic and vascular actions of insulin. This implies that, using this model, there is physiological uncoupling of the effects of insulin in different tissues.

This work was supported by a grant from the British Heart Foundation and a grant from the Wellcome Trust (to C.P.).

Abbreviations: AUC, Area under the curve; CRC, concentration- response curve; NE, norepinephrine; PSS, physiological salt solution.

This article has been cited by other articles:

				P. L. Brubaker Adventure Travel and Type 1 Diabetes: The complicating effects of high altitude Diabetes Care, October 1, 2005; 28(10): 2563 - 2572. [Full Text] [PDF]