CNS NFkappaB Regulation of Glucose Homeostasis

CNS NFkappaB 血糖稳态调节

基本信息

批准号：
8411657
负责人：
Stephanie Renee Sisley
金额：
$ 2.65万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2012-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8411657
关键词：
Acute Address Adipose tissue Adult American Award Basic Science Brain Child Chronic Chronic Disease Clinical Comorbidity Consumption Data Development Diet Dose Environment Euglycemic Clamping Fatty acid glycerol esters Fellowship Funding Glucose Clamp Glucose Intolerance Goals Healthcare Systems Hepatic Hormones Human Hypothalamic structure Immunohistochemistry Inflammation Inflammation Mediators Inflammatory Insulin Insulin Resistance Laboratories Leptin Link Liver Mediating Mentors Metabolic Diseases Metabolism Muscle Non-Insulin-Dependent Diabetes Mellitus Nutrient Obesity Pathway interactions Patients Peripheral Play Prevalence Radioisotopes Rattus Regulation Research Research Technics Rodent Model Role Signal Transduction Skeletal Muscle Societies Sodium Salicylate System Techniques Testing Therapeutic Tissues blood glucose regulation career cost design feeding genetic manipulation glucose output glucose tolerance glucose uptake improved inflammatory marker inhibitor/antagonist insight insulin secretion insulin sensitivity insulin signaling mRNA Expression macrophage novel research study

项目摘要

DESCRIPTION (provided by applicant): Obesity is prevalent in one third of American adults and children and costs the American health care system billions of dollars yearly. The major impact of obesity on patients is the development of obesity-related comorbidities, such as type 2 diabetes mellitus (T2DM). Given the extensive cost to society, as well as the impact of these conditions on patients, establishing the link between obesity and T2DM is paramount to effectively treating and decreasing the prevalence of T2DM. One of the possible mechanisms linking obesity and T2DM is through inflammatory pathways. Accumulating evidence indicates that the CNS is responsive to hormones and nutrients regulating glucose homeostasis and that dysregulation of this system may occur with NF?B activation. However, the potential CNS regulation of this pathway on peripheral metabolic processes has not been studied. In this proposal, Dr. Sisley will focus on the effect of one specific brain inflammatory pathway, NF?B, on glucose homeostasis. Her preliminary data have revealed the ability of a single dose of an NF?B inhibitor to improve glucose tolerance. The specific aims of her proposal will examine the mechanistic link between CNS inhibition of the NF?B pathway on glucose homeostasis using acute inhibition studies. She will also investigate the effect of CNS NF?B inhibition on inflammatory markers in peripheral tissues. The primary goal of this mentored fellowship award is to advance Dr. Sisley forward in her pursuit of an independent research career.

描述（由申请人提供）：三分之一的美国成人和儿童普遍患有肥胖症，每年给美国医疗保健系统造成数十亿美元的损失。肥胖对患者的主要影响是与肥胖相关的合并症的发生，例如 2 型糖尿病 (T2DM)。考虑到社会的巨大成本以及这些疾病对患者的影响，建立肥胖与 T2DM 之间的联系对于有效治疗和降低 T2DM 患病率至关重要。连接肥胖和 T2DM 的可能机制之一是通过炎症途径。越来越多的证据表明，中枢神经系统对调节葡萄糖稳态的激素和营养物质有反应，并且该系统的失调可能会随着 NF?B 的激活而发生。然而，尚未研究该途径对外周代谢过程的潜在中枢神经系统调节作用。在这项提案中，Sisley 博士将重点关注一种特定的大脑炎症途径 NF?B 对葡萄糖稳态的影响。她的初步数据揭示了单剂量 NF?B 抑制剂改善葡萄糖耐量的能力。她提案的具体目标是利用急性抑制研究来检验 CNS 抑制 NF?B 通路与葡萄糖稳态之间的机制联系。她还将研究 CNS NF?B 抑制对外周组织炎症标志物的影响。该指导奖学金的主要目标是推动西斯莱博士追求独立研究事业。