PILOT STUDY IN PHYSIOLOGIC QUANTIFICATION OF INSULIN - RELATED TRAITS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本提案旨在对20名受试者进行胰岛素抑制试验（IST），以获得经验并培训我们的工作人员。IST是一项生理学研究，包括同时输注葡萄糖、胰岛素和奥曲肽3小时。在IST期间，葡萄糖和胰岛素水平达到稳态水平;这允许直接定量胰岛素抵抗和胰岛素清除。这些都是我们将在未来的研究中研究的特征。这项试点研究将通过证明我们有能力执行IST来促进我们的赠款工作。 胰岛素是一种激素，它允许肌肉和脂肪组织从血液中吸收糖（葡萄糖）作为燃料或储存。胰岛素因其在糖尿病中的作用而最为人所知，其中胰岛素作用的缺乏导致血液中非常高的葡萄糖水平和对眼睛、肾脏、神经的损害以及心血管疾病风险的增加。 胰岛素促进葡萄糖摄取能力的缺陷称为胰岛素抵抗。人体通过增加胰腺分泌的胰岛素量来补偿胰岛素抵抗，这一过程称为代偿性高胰岛素血症。影响体内胰岛素量的因素还有胰岛素分泌和胰岛素清除（胰岛素清除是机体消除胰岛素的过程）。胰岛素抵抗和高胰岛素血症被认为是糖尿病以外的许多疾病的基础。这些疾病包括肥胖、代谢综合征和多囊卵巢综合征。所有这些都非常重要，因为它们与糖尿病和心脏病的风险增加有关。胰岛素抵抗或代谢综合征影响美国约25%的成年人，多囊卵巢综合征（PCOS）影响5-7%的育龄妇女。多囊卵巢综合征患者患有排卵障碍和高男性激素称为雄激素。这种疾病的长期后果是不孕症、糖尿病、子宫癌和心脏病。 测量胰岛素抵抗不是一件简单的事情。基于胰岛素和葡萄糖水平的单次血液测试评估的简单测量很容易获得，但是胰岛素抵抗的不精确测量。为了更准确地测量用于研究目的的胰岛素抵抗，需要更复杂的研究，其中研究对象经历几个小时的输注研究。从这些研究中获得的数据可用于获得非常准确的胰岛素抵抗测量。 我们的目标是在Cedars-Sinai建立一个这样的程序，让研究人员进行严格评估胰岛素相关性状的研究。这个过程被称为胰岛素抑制试验（IST）。它包括在三小时内同时输注葡萄糖、胰岛素和生长抑素。在输注结束时出现的葡萄糖和胰岛素水平允许计算胰岛素抵抗和胰岛素清除率。我们建议对20名受试者进行IST，男性或女性，瘦或肥胖，有或没有多囊卵巢综合征，糖尿病或代谢综合征。所获得的经验将用于未来对大量此类受试者的研究，测试有关胰岛素对人类健康和疾病影响的多种假设。

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 purpose of this proposal is to perform the insulin suppression test (IST) in 20 subjects to gain experience and train our staff. The IST is a physiologic study that involves simultaneous infusion of glucose, insulin, and octreotide for 3 hours. During the IST, glucose and insulin levels reach steady state levels; these allow direct quantification of insulin resistance and insulin clearance. These are traits that we will be examining in future research studies. This pilot study will facilitate our grant efforts by demonstrating that we have the ability to perform the IST. Insulin is the hormone that allows muscle and fat tissue to absorb sugar (glucose) from the bloodstream for use as fuel or storage. Insulin is best-known for its role in diabetes mellitus, wherein a deficiency of insulin action leads to very high levels of glucose in the blood and damage to eyes, kidneys, nerves and an increased risk of cardiovascular disease. A defect in insulin¿ s ability to promote glucose uptake is called insulin resistance. The body compensates for insulin resistance by increasing the amount of insulin secreted from the pancreas, a process called compensatory hyperinsulinemia. Factors that also influence the amount of insulin in the body are insulin secretion and insulin clearance (insulin clearance is the process by which the body eliminates insulin). Insulin resistance and hyperinsulinemia are thought to underlie many conditions besides diabetes. These include obesity, the metabolic syndrome, and polycystic ovary syndrome. All of these are very significant because they are associated with an increased risk of developing diabetes and heart disease. The insulin resistance or ¿¿metabolic¿¿ syndrome affects approximately 25% of adults in the U.S., and polycystic ovary syndrome (PCOS) affects 5-7% of reproductive-aged women. Patients with PCOS suffer from defective ovulation and high male hormones called androgens. Long term consequences of this disease are infertility, diabetes, uterine cancer and heart disease. Measurement of insulin resistance is not a simple matter. Simple measurements based on a single blood test assessment of insulin and glucose level are easy to obtain but are imprecise measures of insulin resistance. To more accurately measure insulin resistance for research purposes, more complicated studies are required whereby a study subject undergoes infusion studies over a few hours. The data obtained from such studies can be used to derive very accurate measurements of insulin resistance. Our goal is to establish one such procedure at Cedars-Sinai, to allow researchers to perform studies that critically evaluate insulin-related traits. This procedure is called the Insulin Suppression Test (IST). It involves a simultaneous infusion of glucose, insulin, and the drug somatostatin, over a three-hour period. The levels of glucose and insulin that occur towards the end of the infusion allow calculation of insulin resistance and insulin clearance. We propose to perform the IST on 20 subjects, male or female, lean or obese, and with or without polycystic ovary syndrome, diabetes, or the metabolic syndrome. The experience gained will be utilized in future studies of large numbers of such subjects, testing multiple hypotheses about the impact of insulin in human health and disease.