PPAR ACTIVATION ELEVATES BLOOD PRESSURE AND DOES NOT CORRECT GLUCOCORTICOID

PPAR 激活会导致血压升高，并且不能纠正糖皮质激素

• 批准号: 7721512
• 负责人: SAVITHA SUBRAMANIAN
• 金额: $ 0.44万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721512
• 关键词: Adult; Affect; Ambulatory Blood Pressure Monitoring; Ambulatory Monitoring; Blood Pressure; Blood Vessels; Cholesterol; Computer Retrieval of Information on Scientific Projects Database; Data; Dexamethasone; Dyslipidemias; Euglycemic Clamping; Fasting; Fenofibrate; Fibrates; Funding; Glucocorticoids; Glucose; Glucose Clamp; Grant; Hepatic; Human; Hyperinsulinism; Institution; Insulin; Insulin Resistance; Low-Density Lipoproteins; Nuclear Receptors; Peroxisome Proliferator-Activated Receptors; Placebos; Research; Research Personnel; Resources; Source; Staging; Testing; Triglycerides; United States National Institutes of Health; Vascular Diseases; Weight; day; glucose disposal; glucose production; improved

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 4 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 PPARactivation in humans does not diminish insulin resistance induced by glucocorticoids and may adversely affect blood pressure.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 贝特类，核受体过氧化物酶体激活物，改善血脂异常，但其对胰岛素抵抗和血管疾病的影响尚未解决。为了验证过氧化物酶体增殖物激活物激活能改善胰岛素抵抗和血管功能的假设，我们测定了非诺贝特对短期糖皮质激素诱导的胰岛素抵抗健康成人的影响。在4个阶段研究了18名正常体重受试者：基线时、单独非诺贝特（160 mg/天）21天后、地塞米松（8 mg/天）加非诺贝特3天后和地塞米松加安慰剂3天后（单独地塞米松）。单用地塞米松可引起高胰岛素血症、葡萄糖增加、葡萄糖处置减少和胰岛素诱导的肝葡萄糖生成抑制减少（通过高胰岛素-正葡萄糖钳夹测定），以及收缩压升高（通过动态监测测定），这些特征与胰岛素抵抗状态相关。在地塞米松治疗的情况下，非诺贝特改善了空腹LDL和总胆固醇，但对胰岛素或葡萄糖水平、钳夹期间胰岛素刺激的葡萄糖处置或胰岛素抑制葡萄糖产生或动态监测的血压无显著影响。在没有地塞米松的情况下，非诺贝特降低空腹甘油三酯和胆固醇，但通过动态监测意外地增加收缩压。这些数据表明，人体中的PPAR激活并不能减少糖皮质激素诱导的胰岛素抵抗，并可能对血压产生不利影响。