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: 7476312
• 负责人: Terry P. Combs
• 金额: $ 11.78万
• 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 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7476312
• 关键词: 1-Phosphatidylinositol 3-Kinase; 2,4-thiazolidinedione; 5' -AMP-activated protein kinase; AICA ribonucleotide; Acetyl-CoA Carboxylase; Amino Acids; Binding Proteins; Blood Circulation; Bos taurus; Carbon; Cardiovascular system; Cattle; Cell physiology; Chromosomes; Citric Acid Cycle; Comb animal structure; Complex; Data; Development; Diabetes Mellitus; Disease; Eagles; Equus caballus; Eukaryotic Initiation Factor-4E; Exhibits; Fatty acid glycerol esters; Future; Glucose; Glyceraldehyde 3-Phosphate; Goals; Health; Heart Diseases; Homologous Gene; In Vitro; Individual; Insulin; Insulin Resistance; Intervention; Lead; Leptin; Literature; Liver; Lysosomes; Malignant Neoplasms; Mass Fragmentography; Mediating; Methenamine; Modeling; Obesity; PTEN gene; Pathway interactions; Phosphatidylinositols; Phosphoenolpyruvate Carboxylase; Phosphoric Monoester Hydrolases; Principal Investigator; RNA; Raptors; Research Personnel; Ribosomal Protein S6 Kinase; Role; ST5 Protein; ST5 gene; Serum; Sirolimus; Small Interfering RNA; Testing; Thiazolidinediones; Tissues; adiponectin; fetal; glucose production; glucose-6-phosphatase; human FRAP1 protein; in vivo; inhibitor/antagonist; inorganic phosphate; insight; insulin sensitivity; mTOR protein; malignant breast neoplasm; mutant; obesity treatment; programs; protein degradation; riboside; tensin; vector

DESCRIPTION (provided by applicant): Insulin conserves glucose while insulin resistance reduces the body?s 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 low levels of circulating adiponectin. 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 inhibitor of glucose production, (2) AMPK, a target of adiponectin that inhibits glucose production, (3) lysosome activity, a cellular process of protein degradation that provides 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）：胰岛素保守葡萄糖，而胰岛素抵抗会减少体内葡萄糖的保护。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脂联素的水平较低。我们正在研究增加肝脏中胰岛素敏感性的脂联素途径。我们的具体目标是确定（1）MTOR的作用，（1）MTOR的作用，脂联素和葡萄糖产生的抑制剂的潜在靶标，（2）AMPK，AMPK是脂联素的靶标，脂联素抑制葡萄糖的产生，（3）溶酶体活性，溶酶体活性，一种蛋白质降解的细胞过程，可为氨基酸产生氨基酸。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。

项目成果

Lipopolysaccharide inhibition of glucose production through the Toll-like receptor-4, myeloid differentiation factor 88, and nuclear factor kappa b pathway.

• DOI: 10.1002/hep.22999
• 发表时间: 2009-08
• 期刊: HEPATOLOGY
• 影响因子: 13.5
• 作者: Raetzsch, Carl F.;Brooks, Natasha L.;Alderman, J. McKee;Moore, Kelli S.;Hosick, Peter A.;Klebanov, Simon;Akira, Shizuo;Bear, James E.;Baldwin, Albert S.;Mackman, Nigel;Combs, Terry P.
• 通讯作者: Combs, Terry P.

Adiponectin signaling in the liver.

• DOI: 10.1007/s11154-013-9280-6
• 发表时间: 2014-06
• 期刊: REVIEWS IN ENDOCRINE & METABOLIC DISORDERS
• 影响因子: 8.2
• 作者: Combs, Terry P.;Marliss, Errol B.
• 通讯作者: Marliss, Errol B.