Insulin Control of Fat Regulation and Exercise in Teens

青少年脂肪调节和运动的胰岛素控制

基本信息

批准号：
7257253
负责人：
KRISTEN Jane NADEAU
金额：
$ 13.13万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-07-01 至 2009-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7257253
关键词：
1-Phosphatidylinositol 3-Kinase Address Adipocytes Adipose tissue Adolescent Adult Affect Age Basic Science Biopsy Cardiac Child Childhood Clinical Clinical Research Defect Deposition Development Diabetes Mellitus Echocardiography Euglycemic Clamping Exercise Exercise Physiology Exertion Fatty acid glycerol esters Figs - dietary Functional disorder Glucose Clamp Goals Habits Human Hyperinsulinism Insulin Insulin Resistance Intervention Kinetics Life Style Lipids Measurement Measures Mediating Mentors Morbidity - disease rate Muscle Newly Diagnosed Non-Insulin-Dependent Diabetes Mellitus Nutritional Obesity Pathway interactions Patients Pharmaceutical Preparations Phosphoinositide-3-Kinase, Catalytic, Gamma Polypeptide Population Population Projection Positioning Attribute Randomized Rate Regulation Research Research Personnel Research Training SRE-1 binding protein Signal Transduction Skeletal Muscle Skeletal system Techniques Teenagers Testing Therapeutic Intervention Training Youth basal insulin improved in vivo insulin sensitivity insulin signaling mortality pressure programs response rosiglitazone sedentary

项目摘要

DESCRIPTION (provided by applicant):Type 2 diabetes (T2DM) and obesity are increasing dramatically in pediatric populations, forecasting the development of complications at younger ages, and increased morbidity and mortality in the US population. The proposed research plan will be the first to examine whether the intramyocellular lipid (IMCL) deposition or decreased exercise capacity associated with T2DM in adults already occurs in pediatric T2DM, the underlying mechanism and interrelation of such defects, and how traditional insulin sensitization techniques affect the defects. The hypothesis is that teens with increasing insulin resistance will have increased IMCL (explainable by insulin's selectively impaired PI3-kinase signaling, yet normal Erk signaling, resulting in increased skeletal muscle SREBP-1, yet decreased adipose SREBP-1), decreasing exercise capacity (explainable by endothelial dysfunction, diastolic dysfunction and increased IMCL), and greatest improvement in exercise capacity with interventions that improve both insulin resistance and IMCL deposition. To explore the hypothesis in vivo, we will address the following Specific Aims. 1: Understand the impact of T2DM upon skeletal muscle lipid distribution and SREBP-1 regulation, in comparison to normal adolescents and adolescents with obesity but without T2DM. 2: Determine the baseline exercise capacity and its correlates in adolescents with T2DM in comparison to normal adolescents and adolescents with obesity but without T2DM. 3: Examine the impact of three distinct therapeutic interventions directed at improvement of insulin sensitivity upon responses in SREBP-1 regulation and exercise function, in adolescents with T2DM With the combination of basic science and clinical research training, a clinical research certificate, outstanding mentors in insulin signaling, clinical diabetes research and exercise physiology, I am in an ideal position to be successful. The K-23 application will help me reach my long-term goal of being an independent investigator in the field of pediatric insulin resistance and type 2 diabetes.

描述（由申请人提供）：2型糖尿病（T2DM）和肥胖症在小儿种群中的增长急剧增加，预测了年轻时并发症的发展，并提高了美国人群的发病率和死亡率。拟议的研究计划将是第一个检查成年人已经发生在小儿T2DM中已经发生的成年人中的细胞内脂质（IMCL）沉积或与T2DM相关的运动能力，这是此类缺陷的基本机制和相互关系，以及传统的胰岛素敏化技术如何影响传统的胰岛素敏化技术。缺陷。假设是，胰岛素抵抗增加的青少年将增加IMCL（可以通过胰岛素的有选择性损害的PI3-激酶信号传导（但正常的ERK信号传导）来解释，从而导致骨骼肌SREBP-1，但脂肪SREBP-1降低，降低了运动能力（降低了运动能力）（降低了运动能力（可以通过内皮功能障碍，舒张功能障碍和IMCL增加）来解释，并通过干预措施改善运动能力，从而改善胰岛素抵抗和IMCL沉积。为了探索体内假设，我们将解决以下特定目标。 1：与正常的青少年和肥胖症青少年相比，了解T2DM对骨骼肌脂质分布和SREBP-1调节的影响，但没有T2DM。 2：与正常的青少年和肥胖症青少年相比，确定具有T2DM的青少年的基线运动能力及其相关性，但没有T2DM。 3：检查针对改善胰岛素敏感性对SREBP-1调节和运动功能反应的三种独特的治疗干预措施的影响。胰岛素信号传导，临床糖尿病研究和运动生理学，我是成功的理想位置。 K-23应用将帮助我实现我的长期目标，即成为小儿胰岛素抵抗和2型糖尿病领域的独立研究者。