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

由于糖尿病在老龄人口中占很大比例，因此随着年龄的增长而发生的葡萄糖代谢变化可能在这种疾病的发展中起重要作用。本项目的目的是研究人的葡萄糖代谢调节的年龄差异。胰岛素是一种激素，由称为β细胞的胰腺特殊细胞制造，是葡萄糖的关键调节剂。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影响的见解。将研究三组个体：1）无糖耐量异常的健康老年人，2）葡萄糖耐受不良的健康老年人和3）健康年轻受试者。初步筛选确定了参与研究的资格。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。初始IVGTT后，受试者服用外观相似但无活性的胶囊（安慰剂）或曲格列酮6周。曲格列酮被医生用于治疗糖尿病患者。 它会导致胰岛素敏感性增加，停药后会恢复正常。 在该阶段结束时，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）。随机确定药物/安慰剂的顺序。以双盲交叉方式给予药物，这意味着受试者和研究者均不知道正在给予曲格列酮或安慰剂胶囊，并且每例受试者在研究期间将同时使用药物和安慰剂。在至少两周的洗脱期后，用另一种药物/安慰剂重复上述程序。通过药理学方法实验性诱导胰岛素敏感性的增加，我们将观察这三组中胰腺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.