Therapeutic Adaptation of Insulin Action in Humans

人类胰岛素作用的治疗适应

基本信息

批准号：
7225985
负责人：
ROBERT H. COKER
金额：
$ 13.39万
依托单位：
UNIV OF ARKANSAS FOR MED SCIS
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：
2004-04-01 至 2009-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7225985
关键词：
Address Adenosine Adipocytes Adipose tissue Aerobic Exercise Animal Model Arkansas Attention Body Weight decreased Caloric Restriction Central obesity Clinical Research Commit Cross-Sectional Studies Data Defect Deposition Development Diabetes Mellitus Endocrinologist Endocrinology Energy Intake Energy Metabolism Environment Epidemic Equilibrium Etiology Euglycemic Clamping Exercise Fatty acid glycerol esters Functional disorder Geriatrics Glucagon Glucose Glucose Clamp Goals Hepatic Human Hyperglycemia Hyperinsulinism Incidence Insulin Insulin Resistance Intervention Intramuscular Investigation Laboratories Lipids Liver Longitudinal Studies Medical Mentored Research Scientist Development Award Mentors Metabolic Metabolism Metformin Methodology Molecular Molecular and Cellular Biology National Institute of Diabetes and Digestive and Kidney Diseases Non-Insulin-Dependent Diabetes Mellitus Nonesterified Fatty Acids Numbers OGTT Obesity Overweight Pathogenesis Patients Peripheral Physical activity Prevalence Protein Kinase Public Health Randomized Recommendation Recruitment Activity Research Research Personnel Risk Role Science Scientist Skeletal Muscle Somatostatin Staging Techniques Testing Therapeutic Training Treatment Protocols Triglycerides Universities Visceral Woman Work X-Ray Computed Tomography adiponectin base blood glucose regulation career design diabetes prevention program dietary control dietary restriction experience glucose disposal glucose metabolism glucose production glucose tolerance impaired glucose tolerance improved in vivo insulin sensitivity lipid metabolism longitudinal human study men nutrition obesity treatment older women

项目摘要

DESCRIPTION (provided by applicant): This Mentored Research Scientist Development Award will allow Dr. Coker to extend his work in glucose metabolism performed in animal models into the pathogenesis of insulin resistance in humans. Dr. William J. Evans and Dr. Philip A. Kern will serve as the Co-Mentors for this project. Excessive caloric intake or the lack of physical activity contributes to a positive caloric balance, leading to excess visceral adipose tissue deposition. The pathogenic consequences of visceral obesity usually includes hepatic and skeletal muscle insulin resistance, hyperglycemia, and hyperinsulinemia, and abnormal lipid metabolism eventually leading to type 2 diabetes (T2D). Although caloric restriction and/or exercise training are known to decrease risks associated with T2D, it has been difficult to separate the independent influence of weight loss from exercise training on insulin resistance. We propose to examine the effects of a caloric restriction and/or aerobic exercise training on hepatic and peripheral insulin action using a somatostatin, multi-stage, euglycemic clamp technique in overweight, glucose intolerant men and women. We will recruit 60, 50-80 y old women and men, who will be randomized into one of the following four groups: 1) caloric restriction with weight loss, 2) exercise training without weight loss, 3) exercise training with weight loss, and 4) controls (no dietary or exercise intervention). Dr. Evans has extensive experience in the management of dietary control and exercise training studies. In addition, Dr. Kern will provide specific training in cellular/molecular biology. We will test the hypotheses that 1) caloric restriction will improve hepatic and peripheral insulin action, 2) exercise training without weight loss will only improve peripheral insulin action, 3) exercise training with weight loss will improve hepatic and peripheral insulin action, 4) hepatic insulin action will improve in proportion to the decrease in visceral fat, and that 5) weight loss and exercise training will induce changes in skeletal muscle lipid metabolism through different mechanisms. Since people with impaired glucose tolerance are much more susceptible to the development of T2D, understanding the specific influence of the above mentioned therapeutic regimens on the pathogenesis of insulin resistance has extremely important public health implications. Furthermore, the proposed studies, mentors, co-investigators, and institutional commitment at the University of Arkansas for Medical Sciences provide an outstanding environment for Dr. Coker to develop into an independent basic scientist in diabetes research.

描述（由申请人提供）：这项受过指导的研究科学家发展奖将使科克博士能够将其在动物模型中进行的葡萄糖代谢中的工作扩展到人类胰岛素抵抗的发病机理中。威廉·J·埃文斯（William J. Evans）博士和菲利普·A·克恩（Philip A. Kern）博士将担任该项目的联合体。过量的热量摄入或缺乏体育锻炼会导致热量平衡，导致内脏脂肪组织的过量过量。内脏肥胖的致病后果通常包括肝肌肉胰岛素抵抗，高血糖和高胰岛素血症以及脂质异常代谢，最终导致2型糖尿病（T2D）。尽管已知热量限制和/或运动训练会降低与T2D相关的风险，但很难将体重减轻的独立影响与运动训练对胰岛素抵抗的独立影响。我们建议使用生长抑素，多阶段的多阶段，尤利克利血糖夹在超重，葡萄糖不耐受的男性和女性中，检查热量限制和/或有氧运动训练对肝和周围胰岛素作用的影响。我们将招募60、50-80岁的男女，他们将被随机分为以下四组之一：1）体重减轻的热量限制，2）不体重减轻的运动训练，3）体重减轻的运动训练； 4）控制（无饮食或运动干预）。埃文斯博士在饮食控制和运动培训研究的管理方面拥有丰富的经验。此外，Kern博士将提供特定的细胞/分子生物学培训。我们将测试以下假设：1）热量限制将改善肝和周围胰岛素作用，2）不体重减轻的运动训练只会改善外围胰岛素的作用，3）3）3）体重减轻的运动训练，体重减轻，改善肝和外围胰岛素作用，将改善肝胰岛素动作，4）肝素胰岛素的动作将使骨骼损失和运动量的减少相比，并将其变化。通过不同的机制代谢。由于葡萄糖耐量受损的人更容易受到T2D的发展，因此了解上述治疗方案对胰岛素抵抗发病机理的特定影响具有极为重要的公共健康影响。此外，阿肯色大学医学科学大学的拟议研究，指导者，共同评估者和机构承诺为Coker博士提供了一个杰出的环境，使Coker博士成为糖尿病研究领域的独立基础科学家。