Obesity induced cytokines and beta cell mass regulation

肥胖诱导的细胞因子和β细胞质量调节

基本信息

批准号：
9211315
负责人：
Amelia K Linnemann
金额：
$ 16.3万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2019-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9211315
关键词：
Adult Affect Alpha Cell Apoptosis Apoptotic Beta Cell Biological Assay Biological Preservation Cell Survival Cell physiology Cells Cellular Stress Cellular biology Chemicals Cholecystokinin Clinical Conflict (Psychology)Cytoprotection Data Development Diabetes Mellitus Diabetes prevention Disease Dose Environment Event Future GLP-I receptor Genes Genetic Transcription Glucose Goals High Fat Diet Hormones In Vitro Individual Inflammation Insulin Resistance Interleukin 6 Receptor Interleukin-6 Islet Cell Islets of Langerhans Knock-out Knockout Mice Knowledge Literature LoxP-flanked allele Maintenance Maps Mediating Mentors Metabolic Pathway Metabolism Mollies Mus Non-Insulin-Dependent Diabetes Mellitus Obesity Pathway interactions Peripheral Physiology Prevalence Production Regulation Research Role Scientist Signal Transduction Streptozocin Stress Structure of beta Cell of islet Testing Therapeutic Intervention Thinness Time Training Programs United States Work base biological adaptation to stress career career development cytokine experience glucagon-like peptide 1 in vivo inflammatory marker insulin secretion insulin signaling interest interleukin-6 receptor alpha islet new therapeutic target novel prevent programs public health relevance response stressor therapeutic target transcriptome transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): The goal of this application is to provide Dr. Linnemann with a comprehensive 5-year training program that will allow her to emerge as an independent academic scientist. Through this program she will gain valuable research experience in the fields of islet cell biology, in vivo physiology, obesity, and metabolic pathways Dr. Dawn Belt Davis and Dr. Michael MacDonald will serve as the primary co- mentors for her career and scientific development. Dr. Davis is an emerging leader in the field of diabetes and obesity research. Dr. MacDonald is an established leader in diabetes and metabolism and has a proven track record of mentoring both basic and clinical scientists. Dr. Linnemann has also assembled a mentoring committee comprised of outstanding scientists to provide the full spectrum of career development and scientific guidance. Her mentoring committee includes Dr. Vincent Cryns, Dr. Molly Carnes, and Dr. Michelle Kimple. The research plan involves the study of pancreatic beta cell protection from apoptosis in an obese environment. Obesity is associated with generalized inflammation and an increase in circulating cytokines such as interleukin-6 (IL-6). However, there is conflicting evidence as to the specific role of IL-6 in an obese state. Preliminary data suggests that circulating IL-6 initiates a cascade of intra-islet production of classic gut hormones, namely GLP-1 and cholecystokinin (CCK), that modulate beta cell survival and thus islet mass. Taking this into account, the central hypothesis is that obesity driven IL-6 stimulates adaptive stress response that promotes beta cell function and mass regulation. The specific aims of this application include 1) To determine how a multicomponent IL-6 driven pathway regulates beta cell survival; and 2) To define the in vivo role of IL-6 in obesity driven beta cell mass regulation. Together, these aims will allow the identification of a novel pathway in the protection of beta cells from apoptosis that may serve as a therapeutic target to aid in beta cell mass expansion.

描述（由应用程序提供）：本申请的目的是为Linnemann博士提供全面的5年培训计划，使她能够成为独立的学术科学家。通过该计划，她将在胰岛细胞生物学，体内生理学，肥胖和代谢途径Dawn Belt Davis博士和Michael MacDonald博士的领域获得宝贵的研究经验，并将成为其职业生涯和科学发展的主要院士。戴维斯博士是糖尿病和肥胖研究领域的新兴领导者。 MacDonald博士是糖尿病和代谢领域的知名领导者，在基础科学家和临床科学家方面具有良好的心理记录。 Linnemann博士还组建了一个杰出科学家的心理委员会，以提供各种职业发展和科学指导。她的心理委员会包括Vincent Cryns博士，Molly Carnes博士和Michelle Kinple博士。该研究计划涉及研究肥胖环境中胰腺β细胞保护免受细胞凋亡的研究。肥胖症与全身注射和循环细胞因子（例如白介素6（IL-6））的增加有关。但是，关于IL-6在肥胖状态中的具体作用的证据矛盾。初步数据表明，循环IL-6启动了一系列经典肠道激素的内在产生的级联，即GLP-1和胆囊动蛋白（CCK），从而调节β细胞存活率，从而调节iSLET质量。考虑到这一点，中心假设是拥有驱动IL-6刺激了促进β细胞功能和质量调节的适应性应力反应。本应用程序的具体目的包括1）确定多组分IL-6驱动途径如何调节β细胞存活； 2）定义IL-6在肥胖驱动的β细胞量调节中的体内作用。总之，这些目标将允许在保护β细胞免受细胞凋亡的保护中鉴定新的途径，该途径可能是有助于β细胞质量扩张的治疗靶标。