SERUM GLYCOPROTEIN CHANGES IN THE BB/W DIABETIC RAT

糖尿病的特征是缺乏胰岛素，而且 高血糖(高血糖)，这可能是 与某些碳水化合物异常和许多 疾病的病理影响，包括升高的 几种血清糖蛋白、组织糖蛋白异常 例如基底膜蛋白和改变的细胞表面 淋巴细胞和其他细胞中的糖蛋白。的影响 糖尿病，高血糖或低胰岛素浓度 寡糖的结构和合成尚不清楚。的目的是 这项建议是为了检测血清糖蛋白结构和 BB/W糖尿病大鼠模型的体内外合成 适用于I型(青少年发病)糖尿病。 这里提出的许多研究将集中在结构和 结合珠蛋白的合成，因为我们的初步研究表明 这种糖尿病蛋白显然有一种新的异常 其ASN连接的寡糖。其他研究将包括 对小扁豆-凝集素结合蛋白进行了研究，因为我们的初步研究 研究表明几种BB/W的扁豆-凝集素结合发生了变化 糖尿病大鼠血清糖蛋白。 将对结合珠蛋白和其他血清蛋白进行研究 糖尿病前期、糖尿病控制良好的糖尿病患者体内合成 控制不佳的糖尿病大鼠，以确定 观察到糖蛋白变化与发病的相关性 糖尿病的风险，以及血糖控制的好与差。为了 测定高血糖对糖蛋白生物合成的影响 在体外，结合珠蛋白和其他糖蛋白的合成 在灌流的大鼠肝脏或肝细胞中进行检查 正常或过高的葡萄糖，正常或无胰岛素，模仿 在正常和糖尿病血清中发现的情况。方法： 体内和体内合成的低聚糖的结构分析 体外将包括碳水化合物组成、凝集素亲和力 层析，外切和内切糖苷酶消化，以及 甲基化。

Diabetes mellitus is characterized by a lack of insulin, and by high serum glucose concentrations (hyperglycemia) which can be correlated with some carbohydrate abnormalities and many pathological effects of the disease, including elevated levels of several serum glycoproteins, abnormalities in tissue glycoproteins such as basement membrane proteins, and altered cell surface glycoproteins in lymphocytes and other cells. The effects of diabetes, high glucose or low insulin concentrations on oligosaccharide structure and synthesis are unknown. The aim of this proposal is to examine serum glycoprotein structure and synthesis in vivo and in vitro in the BB/W diabetic rat, a model for type I (juvenile onset) diabetes. Many of the studies proposed here will focus on the structure and synthesis of haptoglobin, since our preliminary studies have shown that this diabetic protein apparently has a novel abnormality in its Asn-linked oligosaccharides. Additional studies will be performed on lentil-lectin binding proteins, since our preliminary studies showed altered lentil-lectin binding of several BB/W diabetic rat serum glycoproteins. Studies will be performed on haptoglobin and other serum proteins synthesized in vivo by prediabetic, well-controlled diabetic and poorly controlled diabetic rats, in order to determine the correlation between the glycoprotein changes observed, the onset of diabetes, and good versus poor glucose control. In order to determine the effects of hyperglycemia on glycoprotein biosynthesis in vitro, synthesis of haptoglobin and other glycoproteins will be examined in perfused rat liver or hepatocytes under conditions of normal or excess glucose, and normal or absent insulin, mimicking conditions found in normal and diabetic serum. Methods of structural analysis of oligosaccharides synthesized in vivo and in vitro will include carbohydrate composition, lectin affinity chromatography, exo- and endoglycosidase digestion, and methylation.