Glucocorticoids and insulin sensitivity: dissociation of insulin's metabolic and vascular actions.
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.
Perry
C G
CG
University Department of Medicine, Western Infirmary, University of Glasgow, Glasgow, Scotland, United Kingdom. colin@fulcrum.u-net.com
Spiers
A
A
Cleland
S J
SJ
Lowe
G D O
GD
Petrie
J R
JR
Connell
J M C
JM
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D001835:Body Weight; D018592:Cross-Over Studies; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000502:physiology; D005215:Fasting / Q000097:blood; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010919:Placebos; D012016:Reference Values; D014661:Vasoconstriction / Q000187:drug effects
D015415:Biomarkers; D005938:Glucocorticoids; D007328:Insulin; D008055:Lipids; D010919:Placebos; D003907:Dexamethasone; D000109:Acetylcholine; D009638:Norepinephrine