AGE EFFECT ON PANCREATIC BETA CELL RESPONSE TO CHANGES IN INSULIN SENSITIVITY

糖尿病在老年人群中占有相当大的比例，随着年龄增长而发生的糖代谢变化可能在糖尿病的发生发展中起重要作用。该项目的目的是研究人体内葡萄糖代谢调节的年龄差异。胰岛素是一种激素，由胰腺中一种叫做β细胞的特殊细胞产生，β细胞是葡萄糖的关键调节器。我们假设胰岛素分泌和适应身体对胰岛素反应变化的细微差异将区分这些群体，并提供有关衰老对这些过程的影响的见解。研究对象分为三组：1)无糖耐量异常的健康老年人，2)糖耐量不耐受的健康老年人，3)健康青年受试者。初步筛选决定参与研究的资格。如果有资格参加，受试者将进行初始静脉葡萄糖耐量试验（IVGTT）以确定身体对胰岛素的敏感性。在最初的IVGTT后，受试者服用一种外观相似但无效的胶囊（安慰剂）或曲格列酮，为期六周。曲格列酮被医生用来治疗糖尿病患者。它会导致胰岛素敏感性增加，停药后会恢复正常。在这段时间结束时，受试者在一天进行另一次IVGTT，并在第二天进行葡萄糖斜坡（一种旨在测量胰岛素分泌的程序）。药物/安慰剂的顺序是随机确定的。药物以双盲交叉方式给予，这意味着受试者和研究者都不知道服用的是曲格列酮还是安慰剂胶囊，并且每个受试者在研究期间将同时服用药物和安慰剂。经过至少两周的洗脱期后，用另一种药物/安慰剂重复上述过程。通过实验诱导胰岛素敏感性的增加，我们将观察这三组胰腺β细胞功能的适应性反应。

As diabetes develops in a significant proportion of the aging population, changes of glucose metabolism occurring with aging may play an important role in the development of this disease. The objective of this project is to study age differences in regulation of glucose metabolism in people. Insulin is a hormone, made by special cells of the pancreas called beta cells, which is a key regulator of glucose. We hypothesize that subtle differences in insulin secretion and adaptation to changes in the body's response to insulin will distinguish these groups and provide insight about the effect aging has on these processes. Three groups of individuals will be studied: 1) healthy elderly with no abnormality of glucose tolerance, 2) healthy elderly with glucose intolerance and 3) healthy young subjects. Initial screening determines eligibility to participate in the study. If eligible to participate, a subject will have an initial intravenous glucose tolerance test (IVGTT) to determine the body's sensitivity to insulin. After the initial IVGTT, the subject takes either a similar appearing but inactive capsule (placebo) or troglitazone for six weeks. Troglitazone is used by physicians to treat people with diabetes mellitus. It causes an increase of insulin sensitivity, which will return to normal after the medication is stopped. At the end of this period, the subjects have another IVGTT on one day and a glucose ramp (a procedure designed to measure insulin secretion) on the following day. The order of drug/placebo is determined randomly. Medication is given in a double-blind crossover manner which means neither the subject nor the investigator knows whether troglitazone or the placebo capsule is being administered and that each subject will have both drug and placebo during the study. Following at least a washout period of at least two weeks, the above procedure is repeated with the other drug/placebo. By experimentally inducing an increase of sensitivity to insulin using pharmacological methods we will observe adaptive response of pancreatic beta cell function in these three groups.