权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Identification of novel genes linking inflammation and insulin signaling

鉴定连接炎症和胰岛素信号传导的新基因

基本信息

批准号：
8562638
负责人：
Michelle L Bland
金额：
$ 28.99万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-02-01 至 2018-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8562638
关键词：
Adipocytes Adipose tissue Affect American Animal Model Animals Applications Grants Categories Communication Data Development Diabetes Mellitus Drosophila genus Drosophila melanogaster Epidemic Fat Body Fatty acid glycerol esters Genes Genetic Genetic Screening Goals Grant Growth Homologous Gene Hormones Human Immune Immune response Immune system Immunosuppression Impairment Individual Infection Inflammation Inflammatory Insulin Insulin Resistance Insulin Signaling Pathway Larva Lead Link Lipids Liver Mammals Mediating Metabolic Muscle Mutation Names Natural Immunity Nature Non-Insulin-Dependent Diabetes Mellitus Nutrient Obesity Organ Pathway interactions Peripheral Phenotype Phosphoric Monoester Hydrolases Phosphorylation Phosphotransferases Prevalence Proteins Regulation Rest Risk Factors Role Signal Transduction Signal Transduction Pathway Testing Tissues Transgenes Transgenic Organisms United States United States National Institutes of Health arm base cytokine falls fly human disease immune activation immune function insulin signaling knock-down macrophage novel novel strategies nutrient metabolism overexpression public health relevance receptor transcription factor

项目摘要

DESCRIPTION (provided by applicant): The increasing prevalence of obesity worldwide has brought with it an epidemic of type 2 diabetes. How an increase in adiposity in obese individuals leads to diabetes is a fundamental, unanswered question. Considerable evidence supports the idea that inflammation of obese adipose tissue impairs insulin action in adipocytes, leading to insulin resistance in muscle and liver. However, it has been difficult to identify additional components that link innate immunity to insulin signaling in humans. In this grant proposal, we describe the use of the genetically-tractable model organism Drosophila melanogaster to employ classical genetics in the identification of such genes. The highly conserved insulin signaling pathway acts in the Drosophila fat body to promote nutrient storage and growth of the whole animal. This organ also serves as th director of the humoral arm of the innate immune response. Remarkably, the interactions between the innate immune and insulin signaling pathways are conserved in Drosophila. Activating innate immune signaling by infection or by transgenic expression of an activated Toll receptor in the fat body leads to decreased phosphorylation of the key downstream component of the insulin signaling pathway, dAkt, and also to decreased growth and viability of the whole animal. The growth impairment and reduced viability resulting frm innate immune suppression of insulin signaling forms the basis for the forward genetic screen proposed here. Already, when performed at a small scale, such an approach has yielded novel regulators of inflammatory and insulin signaling. By performing the proposed genetic screen at a large scale, we aim to identify genes that, when overexpressed or knocked down with the activated Toll receptor in the fat body, reverse the effects of inflammatory signaling on growth. Such genes may encode novel proteins that mediate interactions between the innate immune and insulin signaling pathways, or they may encode molecules that permit the fat body to communicate its nutrient status to the rest of the fly in a manner analogous to the communication between mammalian adipose tissue and peripheral organs. By focusing our studies on genes with clear human orthologues, we hope to identify novel genes that have relevance to human disease.

描述（由申请人提供）：随着全球肥胖症的日益流行，2型糖尿病也随之流行。肥胖是如何增加的