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PPARα activation elevates blood pressure and does not correct glucocorticoid-induced insulin resistance in humans
- Source :
- American Journal of Physiology-Endocrinology and Metabolism. 291:E1365-E1371
- Publication Year :
- 2006
- Publisher :
- American Physiological Society, 2006.
-
Abstract
- Fibrates, activators of the nuclear receptor PPARα, improve dyslipidemia, but their effects on insulin resistance and vascular disease are unresolved. To test the hypothesis that PPARα 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 PPARα activation in humans does not correct insulin resistance induced by glucocorticoids and may adversely affect blood pressure.
- Subjects :
- Adult
Male
medicine.medical_specialty
Physiology
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Blood Pressure
Article
Dexamethasone
Insulin resistance
Fenofibrate
Physiology (medical)
Internal medicine
medicine
Hyperinsulinemia
Humans
PPAR alpha
Glucocorticoids
Hypolipidemic Agents
business.industry
Insulin
Blood Pressure Monitoring, Ambulatory
Glucose clamp technique
medicine.disease
Forearm
Blood pressure
Endocrinology
Regional Blood Flow
Glucose Clamp Technique
Female
Insulin Resistance
Metabolic syndrome
business
Dyslipidemia
medicine.drug
Subjects
Details
- ISSN :
- 15221555 and 01931849
- Volume :
- 291
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Endocrinology and Metabolism
- Accession number :
- edsair.doi.dedup.....09d5b1e6e79bd864197778135cd2cd6b
- Full Text :
- https://doi.org/10.1152/ajpendo.00230.2006