Themis in Type II Diabetes

忒弥斯治疗 II 型糖尿病

• 批准号: 8227228
• 负责人: NICHOLAS R GASCOIGNE
• 金额: $ 28.43万
• 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/8227228
• 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. PUBLIC HEALTH RELEVANCE: The epidemic of obesity and Type II diabetes are becoming extremely important factors to the public health of the US and other developed nations. This project aims to understand the role of T cells in the initiation of the metabolic syndrome that leads to type II diabetes using a new mouse model.

描述（由申请人提供）：Themis（“Thymocyte expressed molecule involved in selection”）是最近发现的基因和蛋白质，其在未成熟胸腺细胞中高度表达，并且在成熟T细胞中也以较低水平表达.它是一个功能未知的小基因家族的成员。Themis缺陷小鼠变得肥胖，并发展葡萄糖耐受不良和血清胰岛素增加，表明Themis表达与预防导致代谢综合征和II型糖尿病（T2D）的脂肪组织炎症之间的关系。T细胞最近被证明在这个过程中很重要。此外，Themis被基因组学鉴定为与血清胰岛素水平存在因果关系，对T2D具有保护作用。该提案将研究Themis在不同谱系的T细胞中的表达如何影响T细胞参与脂肪炎症以响应肥胖和T2D之前的代谢综合征。它将测试代谢综合征和T2D的发展如何因Themis的丧失而加剧，以及作用机制和所涉及的特定T细胞亚群。 公共卫生相关性：肥胖和II型糖尿病的流行正在成为美国和其他发达国家公共健康的极其重要的因素。该项目旨在了解T细胞在代谢综合征引发中的作用，该代谢综合征使用新的小鼠模型导致II型糖尿病。