Proteomic identification of diabetes biomarkers

描述(由申请人提供)：在这项建议中要检验的中心假设是，2型糖尿病的发展导致单核细胞中脂筏的蛋白质组成和脂蛋白的变化。此外，我们假设这些变化将作为糖尿病(糖尿病前期向糖尿病过渡)发展的生物标志物，并作为后续心血管并发症发展的生物标志物。这项建议的目的是阐明与糖耐量正常患者相比，糖耐量受损患者和新诊断的2型糖尿病患者单核细胞脂筏和脂蛋白中的蛋白质发生变化。这项提议的一个独特方面是使用儿科患者。从历史上看，2型糖尿病是一种成人疾病，但不幸的是，越来越多的儿童患有2型糖尿病。虽然成人和儿童的发病机制和进展相似，但成人和儿童患者之间的一个主要区别是儿科患者没有广泛的共病，如动脉粥样硬化、肾功能衰竭和神经病。识别2型糖尿病生物标记物的一个主要问题是患有多种疾病和服用多种药物的患者造成的混淆。在大多数情况下，这些困惑并不是儿科患者的主要问题。出于这些原因，我们选择使用儿科患者。提出了三个具体目标。目的1：阐明正常糖耐量患者的单核细胞和分离的脂蛋白(低密度脂蛋白和高密度脂蛋白)中脂筏的完整蛋白质组。目的2：在单核细胞和从糖耐量受损患者分离的脂蛋白(低密度脂蛋白和高密度脂蛋白)中鉴定与脂筏相关或不相关的蛋白质亚群。目的：研究新诊断的2型糖尿病患者单核细胞和脂蛋白(低密度脂蛋白和高密度脂蛋白)中脂筏蛋白质组的特征。

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.