Themis in Type II Diabetes

忒弥斯治疗 II 型糖尿病

• 批准号: 8438403
• 负责人: NICHOLAS R GASCOIGNE
• 金额: $ 22.86万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-05 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8438403
• 关键词: Adipose tissue; Adoptive Cell Transfers; Affect; Cellularity; Data; Developed Countries; Development; Epidemic; GLUT4 gene; Gene Family; Gene Proteins; Genes; Genomics; Glucose Intolerance; Inflammation; Inflammatory; Inflammatory Response; Insulin; Lymphoid Tissue; Mature T-Lymphocyte; Measures; Membrane; Metabolic; Metabolic syndrome; Metabolism; Methods; Modeling; Mus; Non-Insulin-Dependent Diabetes Mellitus; Obese Mice; Obesity; Pancreas; Plasma; Prevention; Process; Protein Tyrosine Kinase; Public Health; Recruitment Activity; Role; Serum; Syndrome; T-Cell Development; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Thymocyte Selection; Triglycerides; Vertebrates; cytokine; gene discovery; macrophage; member; metabolomics; mouse model; protective effect; response; subcutaneous; thymocyte

DESCRIPTION (provided by applicant): Themis (for "Thymocyte expressed molecule involved in selection") is a recently- discovered gene and protein that is highly expressed in immature thymocytes, and is also expressed at a lower level in mature T cells. It is a member of a small gene family of unknown function. Themis-deficient mice become obese and develop glucose intolerance and increased serum insulin, suggesting a relationship between Themis expression and prevention of the inflammation of adipose tissue that leads to metabolic syndrome and type II diabetes (T2D). T cells have recently been shown to be important in this process. Moreover, Themis was identified by genomics as showing a causal relationship to serum insulin level, with a protective effect against T2D. This proposal will investigate how expression of Themis in T cells of different lineages affects T cell involvement in adipose inflammation in response to obesity, and the metabolic syndrome that precedes T2D. It will test how the metabolic syndrome and development of T2D is exacerbated by loss of Themis, and the mechanism of action and specific T cell subsets involved.

描述(申请人提供)：Themis(胸腺细胞表达的参与选择的分子)是最近发现的一种基因和蛋白，在未成熟的胸腺细胞中高表达，在成熟的T细胞中也低水平表达。它是一个功能未知的小基因家族的成员。Themis基因缺陷的小鼠会变得肥胖，出现糖耐量异常和血清胰岛素增加，这表明Themis的表达与预防脂肪组织炎症之间存在关系，而脂肪组织炎症会导致代谢综合征和II型糖尿病(T2D)。最近，T细胞在这一过程中被证明是重要的。此外，基因组学证实，Themis与血清胰岛素水平存在因果关系，对T2D具有保护作用。这项建议将研究Themis在不同谱系的T细胞中的表达如何影响T细胞参与肥胖反应中的脂肪炎症，以及T2D之前的代谢综合征。它将测试Themis的缺失如何加剧T2D的代谢综合征和发展，以及相关的作用机制和特定的T细胞亚群。