PROTEIN ANALYSIS OF DIABETIC PANCREATIC ISLET AMYLOID

糖尿病胰岛淀粉样蛋白的蛋白质分析

• 批准号: 3232906
• 负责人: GEORGE G GLENNER
• 金额: $ 13.03万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3232906
• 关键词: X ray crystallography; amyloidosis; gel electrophoresis; high performance liquid chromatography; human tissue; immunochemistry; immunoperoxidase; molecular pathology; monoclonal antibody; pancreatic islets; radioimmunoassay

Over 10 million individuals in the United States are affected by diabetes mellitus, the vast majority of these are of Type II (adult onset). A variety of studies have shown that amyloidosis of the islets of Langerhans (AI) occurs in 59 percent of Type II diabetes. It is not seen in diabetics under the age of 40. Its severity is not related to the age of the patient, but is related to the duration and severity of the disease with an incidience of almost 100 percent in Type II insulin-treated diabetics. In such patients the extent of the amyloidosis per islet is correlated with the number of islets involved and in these affected islets the ratio of Beta/Alpha cells is significantly decreased. The localization of AI solely in the islets adjacent to Beta-cells distinguishes it from the localization in the pancreas resulting from systemic amyloidosis. In AI the amyloid fibrils are in close contact with the Beta-cells and the fibrils appear in bundles lying perpendicular to the Beta-cell plasmalemma and often enclosed in invaginations of it suggesting amyloid fibril formation by these cells. Immunohistochemical studies suggest the amyloid fibrils are composed of an insulin-like protein. Attempts to isolate this protein by others have so far been unsuccessful. Since the emyloid fibril protein in AI may provide an important clue as to the nature and cause of Type II diabetes, its isolation and identification would be of great significance. It is proposed that by methods developed by us for the identification of other amyloid fibril proteins, including the use of Sepharose and Sephadex column chromatography in 6 M guanidine, high performance liquid chromatography, immunoabsorbent chromatography, immunohistochemistry and radioimmunoassay, the protein of the amyloid fibrils in AI and its precursor can be identified and its relation to the pathogenesis of Type II diabetes determined. An experimental approach almost identical to that proposed in the enclosed grant application has been used to define the amyloid fibril protein present in the cerebrovascular amyloidosis of Alzheimer's disease.

美国有超过1000万人受到糖尿病的影响 糖尿病，其中绝大多数是II型(成人发病)。一个 各种研究表明，郎格汉斯胰岛的淀粉样变性 (AI)发生在59%的II型糖尿病中。糖尿病患者中不会出现这种情况。 年龄在40岁以下。其严重程度与年龄无关。 患者，但与疾病的持续时间和严重程度有关 II型胰岛素治疗的糖尿病患者的发病率几乎为100%。在……里面 这类患者每个胰岛淀粉样变性的程度与 受影响的胰岛的数量以及在这些受影响的胰岛中 β/α细胞明显减少。人工智能的本土化 在与β细胞相邻的胰岛中区别于定位 全身性淀粉样变性引起的胰腺病变。人工智能中的淀粉样蛋白 纤维与β细胞密切接触，纤维出现在 与β细胞质膜垂直的束状物，通常是封闭的 内陷提示这些细胞形成淀粉样原纤维。 免疫组织化学研究表明淀粉样蛋白纤维由一种 类胰岛素蛋白。其他人分离这种蛋白质的尝试也是如此 但远未成功。 由于AI中的肌样纤维蛋白可能提供了一条重要的线索 II型糖尿病的性质、病因及其分离鉴定 将具有重大意义。有人建议，通过开发的方法 由我们鉴定其他淀粉样原纤维蛋白，包括 琼脂糖凝胶和葡聚糖凝胶柱层析在6-甲基胍中的应用， 高效液相色谱，免疫吸附层析， 免疫组织化学和放射免疫分析，淀粉样蛋白 AI及其前体中的纤维可以被识别，以及它与 II型糖尿病的发病机制已确定。一种实验方法 几乎与所附拨款申请中所建议的相同 被用来定义存在于 阿尔茨海默病的脑血管淀粉样变性。