THE GLUCOSE TRANSPORT SYSTEM AND MECHANISMS OF HUMAN INSULIN RESISTANCE

葡萄糖转运系统和人体胰岛素抵抗机制

• 批准号: 7380430
• 负责人: W Timothy GARVEY
• 金额: $ 0.31万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7380430
• 关键词: GLUCOSE; TRANSPORT; SYSTEM; MECHANISMS; HUMAN

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。胰岛素抵抗综合征（Insulin Resistance Syndrome，INS）是2型糖尿病和心血管疾病发生发展的“共同土壤”，长期的研究目标是找到胰岛素抵抗的环境和遗传因素以及生化或分子基础。胰岛素通过将细胞内GLUT 4葡萄糖转运蛋白易位至细胞表面来刺激葡萄糖转运。NIDDM的胰岛素抵抗是由脂肪中GLUT 4的严重耗竭引起的，而肌肉中GLUT 4的表达是正常的，这表明GLUT 4向质膜的转运可能是有缺陷的。具体目的是检验胰岛素抵抗是由于GLUT 4运输缺陷导致骨骼肌中胰岛素介导的GLUT 4易位受损的假设。为了实现这一点，重要的是包括健康个体沿着胰岛素敏感-抵抗连续体以及2型糖尿病患者。排除的受试者将入住住院GCRC，在那里将进行全面的病史、体格检查、EKG、活动前/活动后血压测量和实验室血液/尿液检查。然后，符合入选标准的个体将接受一次性系列代谢研究，这些研究将表征身体组成、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。