PROTEIN ANALYSIS OF DIABETIC PANCREATIC ISLET AMYLOID

点击翻译按钮获取中文摘要

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.