The effects of adiponectin on liver insulin resistance

脂联素对肝脏胰岛素抵抗的影响

• 批准号: 7133135
• 负责人: Terry P. Combs
• 金额: $ 11.18万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7133135
• 关键词: Krebs' cycle; adiponectin; biological signal transduction; enzyme activity; gluconeogenesis; glucose clamp technique; glucose metabolism; insulin sensitivity /resistance; laboratory mouse; liver; lysosomes; mTOR protein; obesity; protein kinase; small interfering RNA; tissue /cell culture; transfection /expression vector; western blottings

DESCRIPTION (provided by applicant): Insulin conserves glucose while insulin resistance reduces the conservation of glucose. Insulin resistance is associated with many health complications. Many people with insulin resistance develop diabetes. For unknown reasons, insulin resistance also promotes heart disease and breast cancer. Liver insulin resistance increases in the obese state partly because the expansion of fat tissue leads to a low level of adiponectin in the circulation. We are investigating the adiponectin pathway that increases insulin sensitivity in the liver. Our specific goals are to determine the role of (1) mTOR, a potential target of adiponectin and an insulin signaling intermediate that inhibits glucose production, (2) AMPK, a target of adiponectin that inhibits glucose production, (3) lysosome activity, a cellular process of protein degradation that produces amino acids used in gluconeogenesis and (4) the TCA cycle, a major gluconeogenic pathway that uses amino acids for glucose production. The insight we gain could lead to a better understanding of adiponectin action in the liver and more effective interventions for the treatment of insulin resistance.

描述（由申请人提供）： 胰岛素可以保存葡萄糖，而胰岛素抵抗会降低葡萄糖的保存。胰岛素抵抗与许多健康并发症有关。许多患有胰岛素抵抗的人会患上糖尿病。由于未知原因，胰岛素抵抗也促进心脏病和乳腺癌。肥胖状态的肝胰岛素抵抗会增加，部分原因是脂肪组织的膨胀导致循环中脂联素水平较低。我们正在研究增加肝脏中胰岛素敏感性的脂联素途径。 Our specific goals are to determine the role of (1) mTOR, a potential target of adiponectin and an insulin signaling intermediate that inhibits glucose production, (2) AMPK, a target of adiponectin that inhibits glucose production, (3) lysosome activity, a cellular process of protein degradation that produces amino acids used in gluconeogenesis and (4) the TCA cycle, a major gluconeogenic使用氨基酸来生产葡萄糖的途径。我们获得的洞察力可能导致对肝脏中脂联素作用的更好理解，并为治疗胰岛素抵抗的更有效的干预措施。