Studies on Insulin Autoimmune Syndrome

胰岛素自身免疫综合征的研究

• 批准号: 63480274
• 负责人: HIRATA Yukimasa
• 金额: $ 3.58万
• 依托单位: Tokyo Women's Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-63480274/
• 关键词: Insulin; Hypoglycemia; Autoimmunity; Insulin antibody; HLA; SH group; モノクローナル; インスリン自己免疫症候群; 抗イディオタイプ抗体; ハイブリドーマ; HLA抗原タイプ

An etiology of the insulin auto syndrome (IAS) and a mechanism to produce spontaneous severe hypoglycemia in this syndrome have been studied. Clinical data of 148 Japanese patients with IAS were collected from each case report, and insulin and insulin autoantibodies in the sera obtained from some patients among those 148 patients were analyzed in our laboratory.Results were as follows:1. When those 148 patients ( 72 males and 76 females ) were divided into each decade according to the age of onset of their first attack of hypoglycenda, the peak of the number was found in 60 69-year-old. IAS was diagnosed more frequently in the old people than in the young.2. HLA-Bl5(Bw62), Cw4 and DR4 were found much more frequently in the patients with IAS than in Japanese general population.3. HPLC analysis of the extracted insulin from the sera of the patients with IAS revealed the same retention time as that of the synthesized human insulin.4. Scatchard analysis of the insulin autoantibodies in the sera of six patients obtained during the hypoglycemic periods showed the particular dissociation patterns which seemed reasonable to produce the release of insulin from the antibodies.5. Drugs containing a SH group in their molecules, such as methimazole and tiopronin, had been administered before the first attack of IAS at least in 54 among the 148 patients. Those drugs might become one of factors of provocation of insulin autoantibodies. As an experiment in vitro, incubation of insulin with methimazole revealed no change of the nature of insulin which was proved bv HPLC analysis.

本文对胰岛素自身综合征（IAS）的病因和IAS中自发性严重低血糖的发生机制进行了研究。从每个病例报告中收集148例日本IAS患者的临床资料，并在我们的实验室中分析了这148例患者中部分患者血清中的胰岛素和胰岛素自身抗体。当这148名患者（72名男性和76名女性）被分为每十年根据他们的第一次发作的低血糖症的发病年龄，发现在60 69岁的人数的高峰。IAS在老年人中的诊断率高于老年人。IAS患者中HLA-B15（Bw 62）、Cw 4和DR 4的频率明显高于日本普通人群.从IAS患者血清中提取的胰岛素的HPLC分析显示与合成的人胰岛素的保留时间相同. Scatchard分析6例低血糖患者血清中的胰岛素自身抗体，显示出特殊的解离模式，似乎可以合理地从抗体中释放胰岛素.在148名患者中，至少有54名患者在IAS首次发作前服用了分子中含有SH基团的药物，如甲巯咪唑和硫普罗宁。这些药物可能成为诱发胰岛素自身抗体的因素之一。胰岛素与他巴唑孵育的体外实验表明，胰岛素的性质没有改变，这一点已被HPLC分析所证实。