ON THE SUPPRESSION OF PLASMA NONESTERIFIED FATTY ACIDS BY INSULIN DURING

胰岛素对血浆非酯化脂肪酸的抑制作用

• 批准号: 7355161
• 负责人: A Carpentier
• 金额: $ 0.29万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7355161
• 关键词: SUPPRESSION; PLASMA; NONESTERIFIED; FATTY; ACIDS

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. On the suppression of plasma nonesterified fatty acids by insulin during enhanced intravascular lipolysis in humans: During the fasting state, insulin reduces nonesterified fatty acid (NEFA) appearance in the systemic circulation mostly by suppressing intracellular lipolysis in the adipose tissue. In the postprandial state, insulin may also control NEFA appearance through enhanced trapping into the adipose tissue of NEFA derived from intravascular triglyceride lipolysis. To determine the contribution of suppression of intracellular lipolysis in the modulation of plasma NEFA metabolism by insulin during enhanced intravascular triglyceride lipolysis, 10 healthy nonobese subjects underwent pancreatic clamps at fasting vs. high physiological insulin level with intravenous infusion of heparin plus Intralipid. Nicotinic acid was administered orally during the last 2 h of each 4-h clamp to inhibit intracellular lipolysis and assess insulin's effect on plasma NEFA metabolism independently of its effect on intracellular lipolysis. Stable isotope tracers of palmitate, acetate, and glycerol were used to assess plasma NEFA metabolism and total triglyceride lipolysis in each participant. The glycerol appearance rate was similar during fasting vs. high insulin level, but plasma NEFA levels were significantly lowered by insulin. Nicotinic acid significantly blunted the insulin-mediated suppression of plasma palmitate appearance and oxidation rates by 60 and 70%, respectively. In contrast, nicotinic acid did not affect the marked stimulation of palmitate clearance by insulin. Thus most of the insulin-mediated reduction of plasma NEFA appearance and oxidation can be explained by suppression of intracellular lipolysis during enhanced intravascular triglyceride lipolysis in healthy humans. Our results also suggest that insulin may affect plasma NEFA clearance independently of the suppression of intracellular lipolysis.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。在增强的血管内脂解过程中胰岛素对血浆非酯化脂肪酸的抑制：在空腹状态下，胰岛素主要通过抑制脂肪组织中的细胞内脂解来减少体循环中非酯化脂肪酸（NEFA）的出现。在餐后状态下，胰岛素也可以通过增强来自血管内甘油三酯脂解的NEFA进入脂肪组织的捕获来控制NEFA的出现。为了确定在增强的血管内甘油三酯脂解过程中胰岛素对血浆NEFA代谢的调节中细胞内脂解抑制的作用，10名健康非肥胖受试者在空腹与高生理胰岛素水平下静脉输注肝素加Intralidid进行胰腺钳夹。在每个4小时钳夹的最后2小时口服给予烟酸以抑制细胞内脂解，并评估胰岛素对血浆NEFA代谢的影响，而不依赖于其对细胞内脂解的影响。棕榈酸、乙酸和甘油的稳定同位素示踪剂用于评估每位参与者的血浆NEFA代谢和总甘油三酯脂解。空腹与高胰岛素水平时甘油出现率相似，但胰岛素显著降低血浆NEFA水平。烟酸显著减弱了胰岛素介导的血浆棕榈酸盐出现和氧化速率的抑制，分别降低了60%和70%。相反，烟酸不影响胰岛素对棕榈酸清除的显著刺激。因此，大多数胰岛素介导的血浆NEFA出现和氧化的减少可以通过在健康人中增强的血管内甘油三酯脂解期间抑制细胞内脂解来解释。我们的研究结果还表明，胰岛素可能会影响血浆NEFA清除独立的细胞内脂解的抑制。