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Exercise Regulation of Glucose Homeostasis

血糖稳态的运动调节

基本信息

批准号：
8632632
负责人：
LAURIE J GOODYEAR
金额：
$ 36.09万
依托单位：
JOSLIN DIABETES CENTER
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-16 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8632632
关键词：
Actins Acute Adult Children Age-Years Award Body fat Calcium Contracts Data Development Diabetes Mellitus Diabetes prevention Diet Epidemiology Epigenetic Process Exercise Fasting Fatty acid glycerol esters Funding Gene Expression Genomics Glucose Glucose Intolerance Goals Health Health Benefit Healthcare Hepatic Homeostasis Human Incidence Insulin Insulin Resistance Intervention Investigation Laboratories Life Liver Long-Term Effects Mediating Metabolic Metabolism Modification Molecular Mothers Motor Mus Muscle Non-Insulin-Dependent Diabetes Mellitus Obesity Onset of illness Phenotype Phosphotransferases Physical activity Physiological Population Pregnancy Proteins Public Health Regulation Risk Factors Role Science Serum Signaling Protein Skeletal Muscle Technology Testing Tissues Training Translational Research Translations United States Weaning Work World Health Organization blood glucose regulation calmodulin-dependent protein kinase II clinically significant feeding glucose disposal glucose tolerance glucose transport glucose uptake improved insulin sensitivity liver metabolism mouse model muscle metabolism novel nutrition offspring prevent public health relevance response

项目摘要

PROJECT SUMMARY The rates of obesity and type 2 diabetes are increasing at alarming rates in the United States and throughout the world. There is increasing evidence that regular physical activity can prevent or delay the onset of type 2 diabetes, and at least part of the mechanism for these important effects of exercise is the beneficial role of exercise on whole body and tissue glucose homeostasis. The long-term goal of this project is to understand the molecular mechanisms by which exercise exerts beneficial effects on glucose homeostasis and metabolic health. Studies from the current funding cycle of this award have used various mouse models to elucidate novel signaling proteins involved in exercise-stimulated glucose transport including the AMPK-related kinases SNARK, QSK, and BRSK1, the actin motor protein Myo-1c, and the calcium mediated protein CaMKII. The focus of this project for the coming five years is to test the hypothesis that exercise-training before and during pregnancy has profound effects on whole body and tissue insulin sensitivity in adult offspring. While maternal obesity and over-nutrition are established risk factors for obesity and the development of type 2 diabetes in offspring, little is known about the long-term effects of maternal exercise on offspring health. Preliminary mouse studies generated during this funding cycle have shown that maternal exercise can abolish the development of glucose intolerance, increased fasting insulin concentrations, insulin resistance, and increased body fat in offspring at one year of age, even if the mother consumed a high-fat diet. These profound effects of maternal exercise on offspring metabolic health, along with the potential clinical significance of these findings for human health, provide strong rationale for the proposed studies. The overall hypotheses of the proposed work are that maternal exercise improves whole body and tissue glucose homeostasis in offspring and that epigenetic modifications to liver and skeletal muscle mediate these important effects of exercise on glucose homeostasis. There are four specific aims: 1) To determine the effects of maternal exercise on whole body metabolic homeostasis in offspring; 2) To determine if offspring of trained dams have a more advantageous response to dietary and exercise manipulations; 3) To determine the role of the liver in the effects of maternal exercise to improve the metabolic phenotype of offspring; and 4) To determine the role of skeletal muscle in the effects of maternal exercise to improve the metabolic phenotype of offspring. The use of state-of-the art physiological assessments in combination with cutting-edge genomic technologies will provide a powerful approach for elucidation of physiological mechanisms underlying the important effects of maternal exercise on offspring health. Eventual translation of these studies to the human population will be important for worldwide public health.

项目总结