PATHOGENESIS OF DIABETES MELLITUS

糖尿病的发病机制

• 批准号: 3226198
• 负责人: WILLIAM G BLACKARD
• 金额: $ 14.85万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-06-01 至 1988-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3226198
• 关键词: affinity chromatography; affinity labeling; aminoacid; antiantibody; antibody; antibody receptor; antiidiotype antibody; binding proteins; catecholamines; cellular pathology; cholecystokinin; concanavalin A; diabetes mellitus; exocytosis; glucagon; glucocorticoids; glucose; hormone metabolism; hormone regulation /control mechanism; human subject; immunoglobulin idiotypes; insulin; insulin dependent diabetes mellitus; insulin receptor; insulin sensitivity /resistance; ketones; laboratory rat; liver cells; lysosomes; microfilaments; microtubules; nutrition related tag; pancreatic islet function; pancreatic polypeptide; pinocytosis; plasmapheresis; secretin; somatostatin; sulfonylurea; temperature; thyroxine; tissue /cell culture; vesicle /vacuole

A model has been designed to study lysosomal and non-lysosomal processing of insulin by hepatocytes. Attempts to delineate the non-lysosomal pathway will be made. A novel technique to assess emiocytosis of the insulin contained in MVB is to be used to determine the role of emiocytosis in insulin processing. The role of the two or more pathways in receptor recycling will also be assessed. We will examine the effect of a number of factors on processing of insulin. These factors range from a variety of energy fuels to hormones and anti-diabetic drugs. The effect of induced post-receptor defect and diabetic states will also be tested for their effect on insulin processing. A second part of the proposal involves a study of an iatrogenic cause of insulin resistance--insulin antibodies. Studies using plasmapheresis will be performed to determine the role of antibodies in the insulin resistance observed in insulin dependent diabetics. In vivo and in vitro studies will be performed to determine the effect of saturation of insulin antibodies on clearance of antibody. In addition, the role of the liver and hepatocyte Fc receptors on antibody clearance will be studied. Anti-idiotypic antibodies (antibodies to insulin antibodies) will be searched for in plasma of insulin treated diabetic patients. If present, the effect of these antibodies on in vitro systems will be studied to determine if the antibodies inhibit insulin binding to the receptor as well as exhibit insulin-like effects.

已经设计了一个模型来研究溶酶体和非溶酶体处理 肝细胞的胰岛素。 试图描述非赖以生殖体途径 会做。 一种评估胰岛素症状细胞增多症的新技术 MVB中包含的 胰岛素加工。 两种或多个途径在受体中的作用 还将评估回收利用。 我们将研究许多 胰岛素加工的因素。 这些因素范围从多种 能量为激素和抗糖尿病药物燃料。 诱导的效果 受体后缺陷和糖尿病状态也将进行测试 对胰岛素加工的影响。 该提案的第二部分涉及对医源性原因的研究 胰岛素抵抗 - 胰岛素抗体。 使用血浆置换的研究将 进行以确定抗体在胰岛素耐药性中的作用 在胰岛素依赖性糖尿病患者中观察到。 体内和体外研究将 进行以确定胰岛素抗体饱和的影响 清除抗体。 此外，肝脏和肝细胞的作用 将研究抗体清除的FC受体。 抗IDiotypic 将搜索抗体（胰岛素抗体的抗体） 胰岛素治疗的糖尿病患者的血浆。 如果存在， 将研究这些体外系统上的这些抗体 抗体抑制胰岛素与受体的结合以及展示 胰岛素样作用。