PROTEIN ANALYSIS OF DIABETIC PANCREATIC ISLET AMYLOID

在美国，超过1000万人患有糖尿病。 大多数是II型（成人发病）。 一 各种研究表明，胰岛淀粉样变性 (AI)发生在59%的II型糖尿病中。 在糖尿病患者中未见 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相关， 在II型胰岛素治疗的糖尿病患者中几乎100%的发病率。 在 这样的患者，每个胰岛的淀粉样变性程度与 所涉及的胰岛数量以及在这些受影响的胰岛中， β/α细胞明显减少。 人工智能的本地化 在邻近β细胞的胰岛中， 在胰腺中引起的系统性淀粉样变性。 在人工智能中， 原纤维与β细胞紧密接触， 垂直于β细胞质膜的束，通常被包围 内陷表明这些细胞形成淀粉样纤维。 免疫组织化学研究表明，淀粉样纤维是由一个 胰岛素样蛋白。 其他人试图分离这种蛋白质的尝试， 远未成功。 由于AI中的类胚纤维蛋白可能提供了一个重要的线索， II型糖尿病的性质和原因，其分离和鉴定 意义重大 建议通过开发的方法， 用于鉴定其他淀粉样纤维蛋白，包括 在6 M胍中使用Sepharose和Sephadex柱层析， 高效液相色谱，免疫吸附色谱， 免疫组织化学和放射免疫分析，淀粉样蛋白的蛋白质 可以鉴定AI及其前体中的原纤维及其与 II型糖尿病的发病机制确定。 的实验方法 几乎与所附赠款申请中提出的相同， 已经被用来定义淀粉样纤维蛋白存在于 脑血管淀粉样变性的阿尔茨海默病。

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.