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: 6626212
• 负责人: LEONARD C GLASS
• 金额: $ 1.08万
• 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 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6626212
• 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：（由申请人提供）：游离脂肪酸（FFA）紊乱 2型糖尿病的症状有哪些？ 糖尿病个体表现出全天增加的血浆FFA水平。 有趣的是，FFA代谢紊乱在正常葡萄糖 耐受性，胰岛素抵抗，遗传易感的个体， 显性糖尿病的发病，在这些后代中，以及在2型糖尿病中， 在糖尿病受试者中，脂肪组织抵抗 胰岛素这提出了一个有趣的可能性，即FFA作为代谢 信使，当释放量增加时，可损害胰岛素作用 在肌肉和肝脏中，即，“脂毒性。“在目前的赠款中，我们将使用 正血糖胰岛素钳夹与间接量热法结合， 放射性同位素技术和股外侧肌活检，（测量 关键胰岛素信号传导事件），以比较和对比各种 FFA降低剂和FFA氧化抑制剂， 胰岛素介导的肌肉和肝脏葡萄糖代谢，以及脂肪 2型受试者的地形图。