PATHOGENESIS OF DIABETES MELLITUS

已经设计了一个模型来研究溶酶体和非溶酶体的处理 肝细胞分泌胰岛素。试图描绘非溶酶体途径 都会被制造出来。一种评估胰岛素吞噬反应的新技术 MVB中所含的是用来确定红细胞增多症在 胰岛素处理。两条或两条以上途径在受体中的作用 回收利用也将进行评估。我们将研究一些措施的效果 影响胰岛素加工的因素。这些因素包括各种不同的 能量是荷尔蒙和抗糖尿病药物的燃料。诱因的作用 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一种医源性疾病原因的研究 胰岛素抵抗--胰岛素抗体。使用血浆置换的研究将 以确定抗体在胰岛素抵抗中的作用 在胰岛素依赖型糖尿病患者中观察到。体内和体外研究将 以确定胰岛素抗体饱和度对 清除抗体。此外，肝脏和肝细胞的作用 将研究Fc受体对抗体清除的影响。抗独特型 将搜索抗体(针对胰岛素抗体的抗体) 胰岛素治疗的糖尿病患者的血浆。如果存在，则会产生 将对体外系统上的这些抗体进行研究，以确定 抗体抑制胰岛素与受体的结合，并展示 胰岛素样效应。

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.