FFA Metabolism, Insulin Resistance and Type 2 Diabetes

FFA 代谢、胰岛素抵抗和 2 型糖尿病

• 批准号: 6487451
• 负责人: LEONARD C GLASS
• 金额: $ 5.01万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6487451
• 关键词: adult human (21+); biopsy; blood lipid; calorimetry; clinical research; coenzyme A; disease /disorder etiology; fatty acid metabolism; free fatty acids; glucose clamp technique; glucose metabolism; glucose tolerance test; human subject; hypoglycemic agents; insulin sensitivity /resistance; liver metabolism; magnetic resonance imaging; muscle metabolism; noninsulin dependent diabetes mellitus; nuclear magnetic resonance spectroscopy; obesity; pathologic process; patient oriented research; radionuclides

DESCRIPTION: (provided by applicant): Disturbances in free fatty (FFA) metabolism are a characteristic feature of type 2 diabetes mellitus and type 2 diabetic individuals demonstrate daylong increased plasma FFA levels. Interestingly, disturbances in FFA metabolism are observed in normal glucose tolerant, insulin-resistant, genetically predisposed individuals long before the onset of overt diabetes, and in these offspring, as well as in type 2 diabetic subjects, adipose tissue is resistant to the antilipolytic effects of insulin. This raises the interesting possibility that FFA act as metabolic messenger which, when released in increased amounts, can impair insulin action in muscle and liver, i.e., "lipotoxicity." In the present grant we shall use the euglycemic insulin clamp in combination with indirect calorimetry, radioisotope techniques, and vastus lateralis muscle biopsy, (with measurement of key insulin signaling events) to compare and contrast the effects of various FFA lowering agents and inhibitors of FFA oxidation on basal and insulin-mediated muscle and hepatic glucose metabolism, as well as on fat topography in type 2 subjects.

描述：(申请人提供)：游离脂肪紊乱(FFA) 代谢是2型糖尿病和2型糖尿病的特征 糖尿病患者表现出一天内血浆FFA水平升高。 有趣的是，在正常的葡萄糖中观察到游离脂肪酸代谢的紊乱。 耐受性、胰岛素抵抗、遗传易感性的个体很久以前 显性糖尿病的发病，在这些后代中，以及在2型中 糖尿病受试者，脂肪组织具有抵抗降脂作用 胰岛素。这增加了一种有趣的可能性，即游离脂肪酸作为新陈代谢 信使，当释放的量增加时，会削弱胰岛素的作用 在肌肉和肝脏中，即“脂毒性”。在目前的赠款中，我们将使用 正血糖胰岛素钳结合间接量热法， 放射性同位素技术和股外侧肌活组织检查(带测量 关键的胰岛素信号事件)，以比较和对比不同 基础和基础上的FFA降解剂和FFA氧化抑制剂 胰岛素介导的肌肉和肝脏葡萄糖代谢以及对脂肪的影响 第二类受试者的地形图。