RENAL AND CELLULAR STUDIES IN TYPE I DIABETIC PATIENTS

I 型糖尿病患者的肾脏和细胞研究

• 批准号: 7951644
• 负责人: MICHAEL S MAUER
• 金额: $ 0.51万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7951644
• 关键词: Behavior; Biopsy; Blood Pressure; Cells; Clinical; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Cross-Sectional Studies; Cultured Cells; DNA; Development; Diabetic Nephropathy; Electrons; Enzymes; Evaluation; Fibroblasts; Funding; Genetic Variation; Glucose Transporter; Grant; Growth Factor; Hyperglycemia; In Vitro; Individual; Institution; Insulin; Insulin-Dependent Diabetes Mellitus; Kidney; Kidney Failure; Lesion; Link; Longitudinal Studies; Measures; Microscopic; Monozygotic twins; Patients; Phenotype; Process; Research; Research Personnel; Resources; Reverse Transcriptase Polymerase Chain Reaction; Risk; Risk Marker; Siblings; Skin; Sodium-Hydrogen Antiporter; Source; United States National Institutes of Health; base; diabetic; diabetic patient; extracellular; mRNA Expression; non-diabetic; repository; type I diabetic

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. Diabetic nephropathy (DN) is the leading cause of renal failure, yet pathogenetic understanding remains limited. Objectives of these studies are (a) to develop risk markers based on in vitro studies of cells derived from individual insulin dependent diabetic (IDDM) patients, which are related to renal biopsy endpoints, (b) to ask if these markers represent genetically determined processes and (c) to define relationships between cellular (in vitro) expression of mRNA for extracellular martix (ECM) molecules, their enzymes and enzyme regulators, growth factors, glucose transporters, and sodium/hydrogen antiporter and renal structural and functional endpoints in order to explore basic pathogenic mechanisms in DN; to develop a repository of DNA and cultured cells that will allow evaluation of the cellular functional consequences of genetic variations shown to be linked to DN risk. Three patient groups will be studied: (a) early (~10 years) and long-term (~20 years) IDDM duration patients dichotomized into 2 groups with slow or rapid development of DM lesions, (b) sibling pairs concordant for IDDM, and (c) identical twins discordant for IDDM. DN will be quantitated morphometrically, and factored for duration or expressed as a rate determined by 2 biopsies 5 years apart. The primary endpoint will be mesangial volume fraction [Vv(Mes/glom)] measured by electron microscopic morphometric analysis. Cross-sectional studies of long-term IDDM patients will allow the identification of cellular markers associated with very rapid or very slow development of DN lesions and clinical renal abnormalities. Longitudinal studies (5 year) in shorter-term "fast" and "slow-track" patients and IDDM sibling pairs will allow factoring for glycemia and blood pressure and other "environmental variables." Cultured skin fibroblasts (SF) from individual patients will be evaluated for mRNA expression for the above listed molecules using reverse transcriptase polymerase chain reaction. SF are selected since changes in their phenotype occur in "fast-track" IDDM patients and are correlated in sibling pairs. These studies will determine the relationship of DN lesions to SF behavior and evaluate whether this behavior is concordant in IDDM sibling pairs who are concordant for DN lesions. SF from nondiabetic identical twins will answer whether hyperglycemia is necessary for the expression of cellular markers of DN risk.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 糖尿病性肾病（DN）是肾衰竭的主要原因，但致病理解仍然有限。 Objectives of these studies are (a) to develop risk markers based on in vitro studies of cells derived from individual insulin dependent diabetic (IDDM) patients, which are related to renal biopsy endpoints, (b) to ask if these markers represent genetically determined processes and (c) to define relationships between cellular (in vitro) expression of mRNA for extracellular martix (ECM) molecules, their enzymes and enzyme调节剂，生长因子，葡萄糖转运蛋白以及钠/氢抗毒剂以及肾脏结构和功能终点，以探索DN中的基本致病机制；开发DNA和培养细胞的存储库，以评估显示与DN风险相关的遗传变异的细胞功能后果。 将研究三个患者组：（a）早期（约10年）和长期（约20年）IDDM持续时间患者将DM病变的缓慢或快速发育分为2组，（b）IDDM的同胞配对，以及（c）与IDDM不同化的相同的双胞胎。 DN将通过形态计量进行定量，并考虑持续时间，或以相距5年的2个活检确定的速度表示。 主要终点将是通过电子显微镜形态计量分析测量的膜膜体积分数[VV（MES/GLOM）]。 长期IDDM患者的横断面研究将允许鉴定与DN病变和临床肾脏异常发育相关或非常缓慢发展的细胞标记。 在短期“快速”和“慢轨”患者和IDDM兄弟姐妹对中进行的纵向研究（5年）将允许考虑血压和血压以及其他“环境变量”的考虑。 使用逆转录酶聚合酶链反应，将评估来自个别患者的培养的皮肤成纤维细胞（SF）的mRNA表达。 选择了SF，因为其表型的变化发生在“快速轨道” IDDM患者中，并以同胞对相关。 这些研究将确定DN病变与SF行为的关系，并评估这种行为是否与DN病变一致的IDDM同胞对中。 非糖尿病相同双胞胎的SF将回答是否需要高血糖表达DN风险的细胞标记。