IN VIVO STUDIES OF INSULIN RESISTANCE IN FAMILIES OF PATIENTS WITH NIDDM

这项研究的一个目标是检验胰岛素的假设 抵抗是非胰岛素依赖型患者的基本缺陷 糖尿病(NIDDM)，并有遗传基础。因此， 我们将量化胰岛素的作用(胰岛素刺激的葡萄糖 葡萄糖钳夹技术处理)和胰岛素分泌 静脉和口服葡萄糖的胰岛素释放和 混合液体餐)在四组明确定义的个体中 以及他们的一级亲属。这四个小组将由 研究对象：1)相对胰岛素敏感的非糖尿病受试者；2) 相对胰岛素抵抗的非糖尿病受试者；3)胰岛素 糖耐量低减患者缺乏糖耐量 空腹高血糖；4)NIDDM和显著 空腹高血糖。第二个目标是使用这四个索引 与人口及其家庭成员进行合作研究 其他四名调查人员正在努力界定 观察到的胰岛素分泌和胰岛素分泌变化的发病机制 行动。这些实验将涉及以下内容：1)使用 新鲜分离的单核细胞、脂肪细胞和培养的淋巴细胞 研究胰岛素受体动力学、生物合成和激酶 活性和胰岛素对生物功能的作用(Dr。 Goldfiny)；2)限制性片段长度多态性分析 探索胰岛素、胰岛素样生长因子、胰岛素的基因 受体和葡萄糖转运体(Karam博士，3)测量 血浆缩胆囊素及其关系的定义 对不同人群的胰岛素分泌反应 (利德尔博士)；4)探索葡萄糖诱导的作用 胰岛素分泌缺陷患者的脱敏治疗 NIDDM(Grodsky博士)；以及5)是否存在循环肽 血浆提取物中存在的物质可以调节胰岛素的释放 灌流的大鼠胰岛，以及这些肽在 NIDDM(格罗茨基博士)。

One goal of this study is to test the hypothesis that insulin resistance is a basic defect in patients with non-insulin dependent diabetes mellitus (NIDDM), and has a genetic basis. Consequently, we will quantitate insulin action (insulin-stimulated glucose disposal by the glucose clamp technique) and insulin secretion {insulin release in response to intravenous and oral glucose and a mixed liquid meal) in four well-defined groups of individuals and their first-degree relatives. These four groups will consist of: 1) relatively insulin sensitive nondiabetic subjects; 2) relatively insulin resistant nondiabetic subjects; 3) insulin resistant patients with glucose intolerance in the absence of fasting hyperglycemia; and 4) patients with NIDDM and significant fasting hyperglycemia. A second goal is to use these four index populations and their family members for collaborative studies with the other four investigators in an effort to define the pathogenesis of the observed changes in insulin secretion and action. These experiments will involve the following: 1) Use of freshly isolated monocytes, adipocytes, and cultured lymphocytes to study both insulin receptor dynamics, biosynthesis, and kinase activity, and insulin action on biological functions (Dr. Goldfine); 2) Restriction fragment length polymorphism analysis to probe the genes for insulin, insulin like growth factors, insulin receptor and the glucose transporter (Dr. Karam; 3) Measurements of plasma cholecystokinin and the definition of its relationship to the insulin secretory response of the various population groups (Dr. Liddle); 4) Exploration of the role of glucose-induced desensitization in the defects of insulin secretion in patients with NIDDM (Dr. Grodsky); and 5) Whether, circulating peptides present in plasma extracts can regulate insulin release from perfused rat islets, and whether these peptides are altered in NIDDM (Dr. Grodsky).