Proteomic identification of diabetes biomarkers

糖尿病生物标志物的蛋白质组学鉴定

• 批准号: 7268126
• 负责人: Eric J Smart
• 金额: $ 17.78万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7268126
• 关键词: Adult; Affect; Atherosclerosis; Biological Markers; Blindness; Cardiovascular Diseases; Cardiovascular system; Cell physiology; Child; Childhood; Development; Diabetes Mellitus; Disease; Disease Progression; Disruption; Goals; Heart Diseases; High Blood Pressure; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Inflammatory; Kidney Failure; Lipoproteins; Low-Density Lipoproteins; Membrane Microdomains; Modification; Morbidity - disease rate; Nerve; Neuropathy; Newly Diagnosed; Non-Insulin-Dependent Diabetes Mellitus; Numbers; Pathway interactions; Patients; Pharmaceutical Preparations; Play; Proteins; Proteome; Proteomics; Risk; Risk Factors; Role; Signal Transduction; Stroke; System; Testing; cardiovascular disorder risk; diabetic; glucose tolerance; impaired glucose tolerance; macrophage; monocyte; non-diabetic; particle

DESCRIPTION (provided by applicant): The central hypothesis to be tested in this proposal is that the development of Type 2 diabetes induces alterations in the protein composition of lipid rafts in monocytes and in lipoproteins. Furthermore, we hypothesize that these changes will serve as biomarkers for both the development of diabetes (pre-diabetic to diabetic transition) and serve as biomarkers for the development of subsequent cardiovascular complications. The goal of this proposal is to elucidate proteins that are altered in monocyte lipid rafts and lipoproteins in patients with impaired glucose tolerance and newly diagnosed type 2 diabetics compared to patients with normal glucose tolerance. A unique aspect of this proposal is the use of pediatric patients. Type 2 diabetes has historically been an adult disease but unfortunately a large and growing number of children have type 2 diabetes. Although the mechanisms and progression of the disease appear similar in adults and children, a major difference between adult and pediatric patients is that the pediatric patients do not have as extensive co-morbidities such as atherosclerosis, renal failure, and neuropathy. A major problem in identifying biomarkers for type 2 diabetes are confounds created by patients having multiple diseases and taking multiple medications. For the most part these confound is not a major problem in pediatric patients. For these reasons, we have chosen to use pediatric patients. Three Specific Aims are proposed. Aim 1: To elucidate the complete proteome of lipid rafts in monocytes and in isolated lipoproteins (LDL and HDL) isolated from patients with normal glucose tolerance. Aim 2: To identify a subset of proteins that associate or disassociate with lipid rafts in monocytes and in lipoproteins (LDL and HDL) isolated from patients with impaired glucose tolerance. Aim 3: To characterize the proteome of lipid rafts in monocytes and in lipoproteins (LDL and HDL) isolated from newly diagnosed Type 2 diabetics.

描述（由申请人提供）：该提案中要检验的中心假设是2型糖尿病的发展诱导单核细胞和脂蛋白中脂质筏的蛋白质组成改变。此外，我们假设这些变化将作为糖尿病发展（糖尿病前与糖尿病过渡）的生物标志物，并用作发展随后的心血管并发症的生物标志物。该提案的目的是阐明与正常葡萄糖耐量的患者相比，葡萄糖耐受性受损和新诊断的2型糖尿病患者的单核细胞脂肪和脂蛋白改变的蛋白质。该提案的一个独特方面是使用小儿患者。 2型糖尿病历史上一直是成人疾病，但不幸的是，越来越多的儿童患有2型糖尿病。尽管在成人和儿童中，疾病的机制和进展似乎相似，但成年和儿科患者之间的主要区别在于，小儿患者的合并症不如动脉粥样硬化，肾衰竭，肾衰竭和神经病。鉴定2型糖尿病生物标志物的主要问题是患有多种疾病并服用多种药物的患者产生的混杂。在大多数情况下，这些混淆不是小儿患者的主要问题。由于这些原因，我们选择使用儿科患者。提出了三个具体目标。目标1：阐明单核细胞中脂质筏的完整蛋白质组以及从具有正常葡萄糖耐受性的患者中分离出的分离的脂蛋白（LDL和HDL）。目标2：确定与单核细胞中的脂肪筏或分离的蛋白质的子集以及从葡萄糖耐受性受损的患者中分离出的脂蛋白和脂蛋白（LDL和HDL）中的子集。目标3：表征单核细胞中脂质筏的蛋白质组和从新诊断的2型糖尿病患者中分离出的脂蛋白（LDL和HDL）中的蛋白质组。