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

由于糖尿病在老年人群中占相当大的比例，随着年龄的增长，糖代谢的变化可能在该病的发展中发挥重要作用。这个项目的目的是研究人们在调节葡萄糖代谢方面的年龄差异。胰岛素是一种荷尔蒙，由胰腺中被称为β细胞的特殊细胞制造，它是血糖的关键调节因素。我们假设，胰岛素分泌的细微差异和对身体对胰岛素反应变化的适应将区分这些群体，并提供关于衰老对这些过程的影响的洞察力。将研究三组人：1)没有糖耐量异常的健康老年人，2)有糖耐量异常的健康老年人和3)健康的年轻人。初步筛选确定是否有资格参加这项研究。如果有资格参加，受试者将接受初步的静脉葡萄糖耐量测试(IVGTT)，以确定身体对胰岛素的敏感性。在最初的IVGTT之后，受试者要么服用类似的无活性胶囊(安慰剂)，要么服用烟酸两周。烟酸是医生用来治疗高血脂患者的药物。它还会导致胰岛素敏感性的暂时下降，在药物停止后，胰岛素敏感性将恢复正常。在这段时间结束时，受试者在第二天进行另一次IVGTT，并在第二天进行葡萄糖梯度(一种用于测量胰岛素分泌的程序)。药物/安慰剂的顺序是随机确定的。药物是以双盲交叉的方式给予的，这意味着受试者和研究人员都不知道是在服用烟酸还是安慰剂胶囊，而且在研究期间每个受试者都将同时服用药物和安慰剂。在至少两周的洗脱期之后，对另一种药物/安慰剂重复上述过程。通过使用药理学方法通过实验诱导胰岛素敏感性下降，我们将观察实验诱导的胰岛素抵抗对这三组人胰岛β细胞功能的影响。

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 nicotinic acid for two weeks. Nicotinic acid is used by physicians to treat people with high blood fat levels. It also causes a temporary decrease in 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 nicotinic acid 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 a decline of sensitivity to insulin using pharmacological methods we will observe the impact of experimentally induced insulin resistance on pancreatic beta cell function in these three groups.