THE GLUCOSE TRANSPORT SYSTEM AND MECHANISMS OF HUMAN INSULIN RESISTANCE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。胰岛素抵抗综合征为2型糖尿病和心血管疾病的发展提供了“共同土壤”。长期目标是必须找到环境和遗传决定因素以及胰岛素抵抗的生化或分子基础。胰岛素通过细胞内GLUT4葡萄糖转运蛋白转运到细胞表面来刺激葡萄糖转运。NIDDM患者的胰岛素抵抗是由脂肪中GLUT4的大量消耗引起的，而在肌肉中GLUT4的表达是正常的，这表明GLUT4向质膜的易位可能存在缺陷。具体目的是验证胰岛素抵抗是由于GLUT4运输缺陷导致的，这损害了胰岛素介导的GLUT4在骨骼肌中的易位。为了实现这一目标，包括胰岛素敏感-抵抗连续体的健康个体以及2型糖尿病患者将是很重要的。同意的受试者将被送入住院GCRC，在那里将进行全面的病史、体格检查、心电图、活动前/后血压测量和实验室血液/尿液检测。符合入组标准的个体将接受一次性的代谢研究，包括身体组成、能量消耗、葡萄糖耐量、体内胰岛素敏感性、体内葡萄糖代谢、胰岛素分泌和脂质代谢。入院时间不应超过5至7天。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Insulin Resistance Syndrome provides the "common soil" for the development of Type 2 Diabetes Mellitus and Cardiovascular Disease.The long-term objective is the necessity of finding the environmental and genetic determinants together with the biochemical or molecular basis of this insulin resistance. Insulin stimulates glucose transport via translocation of intracellular GLUT4 glucose transporters to the cell surface. Insulin resistance in NIDDM is caused by profound depletion of GLUT4 in fat, while in muscle GLUT4 expression is normal, suggesting that GLUT4 translocation to the plasma membrane may be defective. The specific aim is to test the hypothesis that insulin resistance is due to defects in GLUT4 trafficking which impair insulin-mediated GLUT4 translocation in skeletal muscle. In order to accomplish this, it will be important to include healthy individuals along the insulin sensitive-resistant continuum as well as type 2 diabetics. Consented subjects will be admitted to the inpatient GCRC where a thorough medical history, physical examination, EKG, pre/post activity blood pressure measurements, and laboratory blood/urine testing will be performed. Individuals meeting entry criteria will then undergo a one-time series of metabolic studies that will characterize body composition, energy expenditure, glucose tolerance, in-vivo insulin sensitivity, in-vivo glucose metabolism, insulin secretion, and lipid metabolism. Admission should not exceed 5 to 7 days.