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This Article Full Text Full Text (PDF) All Versions of this Article: 291/6/E1365    most recent 00230.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Subramanian, S. Articles by Semenkovich, C. F. Search for Related Content PubMed PubMed Citation Articles by Subramanian, S. Articles by Semenkovich, C. F.

PPAR activation elevates blood pressure and does not correct glucocorticoid-induced insulin resistance in humans

¹Endocrinology, Metabolism, and Lipid Research, Department of Medicine, and ²Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri

Submitted 16 May 2006 ; accepted in final form 19 July 2006

Fibrates, activators of the nuclear receptor PPAR, improve dyslipidemia, but their effects on insulin resistance and vascular disease are unresolved. To test the hypothesis that PPAR activation improves insulin resistance and vascular function, we determined the effects of fenofibrate in healthy adults with insulin resistance induced by short-term glucocorticoid administration. Eighteen normal-weight subjects were studied in four stages: at baseline, after 21 days of fenofibrate (160 mg/day) alone, after 3 days of dexamethasone (8 mg/day) added to fenofibrate, and after 3 days of dexamethasone added to placebo (dexamethasone alone). Dexamethasone alone caused hyperinsulinemia, increased glucose, decreased glucose disposal, and reduced insulin-induced suppression of hepatic glucose production as determined by hyperinsulinemic euglycemic clamp and increased systolic blood pressure as determined by ambulatory monitoring, features associated with an insulin-resistant state. Fenofibrate improved fasting LDL and total cholesterol in the setting of dexamethasone treatment but had no significant effect on levels of insulin or glucose, insulin-stimulated glucose disposal, or insulin suppression of glucose production during clamps, or ambulatory monitored blood pressure. In the absence of dexamethasone, fenofibrate lowered fasting triglycerides and cholesterol but unexpectedly increased systolic blood pressure by ambulatory monitoring. These data suggest that PPAR activation in humans does not correct insulin resistance induced by glucocorticoids and may adversely affect blood pressure.

peroxisome proliferator-activated receptor-; dexamethasone; insulin sensitivity; metabolic syndrome

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