Journal
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Volume 291, Issue 6, Pages E1365-E1371Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00230.2006
Keywords
peroxisome proliferator-activated receptor-alpha; dexamethasone; insulin sensitivity; metabolic syndrome
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Funding
- NCRR NIH HHS [P41-RR-00095, M01-RR-00036, P41 RR000954, M01 RR000036] Funding Source: Medline
- NHLBI NIH HHS [P50 HL083762, P50-HL-083762] Funding Source: Medline
- NIDDK NIH HHS [P50-DK-20579, F32-DK-066977, P30 DK056341-05S2, P60 DK020579, P30 DK056341, P30 DK056341-06, F32 DK066977] Funding Source: Medline
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PPAR alpha activation elevates blood pressure and does not correct glucocorticoid-induced insulin resistance in humans. Am J Physiol Endocrinol Metab 291: E1365-E1371, 2006. First published July 25, 2006; doi:10.1152/ajpendo.00230.2006. Fibrates, activators of the nuclear receptor PPAR alpha, improve dyslipidemia, but their effects on insulin resistance and vascular disease are unresolved. To test the hypothesis that PPAR alpha 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 alpha activation in humans does not correct insulin resistance induced by glucocorticoids and may adversely affect blood pressure.
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