mechanism of insulin autoantibody production for pathogenesis of pancreatic beta cell destruction and hyperplasia

胰岛素自身免疫综合征(IAS)和1型糖尿病均以胰岛素自身抗体为特征。另一方面，胰岛素抗体或抗胰岛素抗体是一种皮下注射的抗胰岛素抗体。胰岛素抗体和胰岛素自身抗体都具有结合人血清中胰岛素的能力。自1970年Hirata报道以来，我们在日本收集了244例胰岛素自身免疫综合征(IAS)患者的记录，截至1997年，平均每年发生9例IAS患者。收集1998~1999年IAS患者11例，2000年~2003年IAS患者19例。国际会计准则的发展没有增加。2003年底共收集了274例胰岛素自身免疫综合征患者。38%的患者在IAS发生前接受了他巴唑、硫代巴比妥钠和硫酮等羟基化合物的治疗。从IAS的发病率来看，没有逐年增加的趋势。部分患者在发生IAS后出现餐后高血糖。收集糖耐量试验(GTT)结果。其中59%为糖尿病型，38%为糖耐量低减。这表明大约90%的人表现出异常的糖代谢。用125I-人胰岛素对胰岛素自身抗体进行Scatchard分析。胰岛素自身抗体的主要部分是高亲和力(K1)-低容量(B1)位点，并与胰岛素治疗的糖尿病患者中发现的胰岛素抗体位点进行了比较。胰岛素治疗的糖尿病患者K1和b1分别大于1×10~(-8)L/m ol和1×10~(-8)m o l/L左右，而胰岛素依赖型糖尿病患者分别小于1×10~(-8)L/m o l和>1×10~(-8)m o l/L。有显著差异(p&lt；0.001)。

Both of insulin autoimmune syndrome (IAS) and type 1 diabetes are characterized by insulin autoantibody. On the other hand, insulin antibody or anti-insulin antibody is a antibody against insulin which is injected subcutaneously. The insulin antibody and the insulin autoantibody have both an ability to bind insulin in human serum. Since reported by Hirata in 1970, we collected 244 patient record with insulin autoimmune syndrome (IAS) in Japan until 1997, which showed a development of averaged 9 patients with IAS per year. We collected 11 patients with IAS from 1998 to 1999, and collected 19 patients with IAS from 2000 to 2003. There was no increase of the development of IAS. Total of 274 patients with insulin autoimmune syndrome were collected in the end of 2003. Thirty-eight % of them was treated with sulfhydroxy compounds such as Methimazole, Thiola and Tathione before the development of IAS. According to the incidence of IAS, there was no increase year by year. Some of the patients had postprandial hyperglycemia after the development of IAS. the outcome of glucose tolerance test (GTT) was collected. Among them who were performed GTT, 59% had diabetic pattern, 38% had IGT pattern. It suggests that approximately 90% showed abnormal glucose metabolism. The characterization of the insulin autoantibody was done by Scatchard analysis using 125 I-human insulin. A major part of the insulin autoantibody was a high affinity (k1)-low capacity (b1) site, the site was compared with that of insulin antibody which were found in insulin-treated diabetic patients. The k1 and b1 were more than 1x10^8 L/mol and around 1 or less than 1x10^8 mol/L, respectively in insulin-treated diabetic patients, whereas those were less than 1x10^8 L/mol and more than 1x10^8 mol/L, respectively in the patients with IAS. There was a significant difference (p<0.001).