DETERMINATION OF METFORMIN AND INSULIN EFFECT ON HEPATIC TRIGLYCERIDE CONTENT

二甲双胍和胰岛素对肝甘油三酯含量影响的测定

• 批准号: 7377644
• 负责人: JEFFREY D BROWNING
• 金额: $ 0.94万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377644
• 关键词: DETERMINATION; METFORMIN; INSULIN; EFFECT; HEPATIC

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. Fatty infiltration of the liver can occur by four distinct mechanisms: 1) increased flux of fatty acids to the liver; 2) increased synthesis of fatty acids in hepatocytes; 3) decreased hepatocyte secretion of fatty acids in the form of very-low-density-lipoprotein and; 4) decreased oxidation of fatty acids by hepatocytes. Animal models suggest that de novo synthesis of fatty acids plays a significant role in the accumulation of liver fat in the setting of insulin resistance. Importantly, the level of fatty acid synthesis in the liver is a function of circulating insulin levels, even in the setting of hepatocyte insulin resistance. One would expect that as insulin resistance worsens and insulin levels rise (either as a result of increased pancreatic islet cell output or supplementation with exogenous insulin), so to would the rate of hepatocyte fatty acid synthesis. This could potentially increase the liver fat content. Investigators in the study propose to examine the effect of two current standard care therapies for type 2 diabetes mellitus on liver fat content: metformin and insulin. Liver fat content will be assessed using proton magnetic resonance spectroscopy before and after 4 months of therapy. Subjects will be randomly assigned to one of the two medication to be studied and closely monitored for any drug-specific toxicities associated with their use.

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。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。肝脏的脂肪浸润可以通过四种不同的机制发生：1）脂肪酸向肝脏的通量增加； 2）增加肝细胞中脂肪酸的合成； 3）以非常低密度脂蛋白的形式降低脂肪酸的肝细胞分泌； 4）肝细胞减少脂肪酸的氧化。动物模型表明，在胰岛素抵抗的情况下，从头合成脂肪酸在肝脏脂肪的积累中起着重要作用。重要的是，即使在肝细胞胰岛素抵抗的情况下，肝脏中脂肪酸合成的水平也是循环胰岛素水平的函数。人们会期望，随着胰岛素抵抗的恶化，胰岛素水平升高（胰岛细胞输出增加或用外源胰岛素补充的结果），因此，肝细胞脂肪酸合成的速率也会增加。这可能会增加肝脏脂肪含量。 研究人员在研究中建议检查两种当前标准护理疗法对2型糖尿病对肝脏脂肪含量的影响：二甲双胍和胰岛素。在治疗4个月之前和之后，将使用质子磁共振光谱法评估肝脂肪含量。受试者将被随机分配到两种药物之一，以进行研究并密切监测与使用相关的任何药物特异性毒性。