| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1989: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1988: ¥800,000 (Direct Cost: ¥800,000)
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| Research Abstract |
The immune mechanism for generation of insulin antibodies in the insulin autoinunune syndrome is unclear. We intended to clarify : 1) whether the circulating insulin in the patients with this syndrome is abnormal, 2) whether sulfhydryl (SH) group - containing drugs can alter the structure of insulin and its cell receptors, and 3) whether certain HLA-types relate to these patients with the syndrome. When free insulin extracted from plasma by acid gel chromatography was applied to reverse phase HPLC, a major insulin peak emerged with the same retention time as standard human insulin in all studied patients with this syndrome. In addition, a minor immunoreactive insulin was consistently found at relatively high acetonitrile concentrations. However, this hydrophobic insulin was also found in insulin-treated diabetic patients and in hyperinsulinemic patients who did not have insulin antibodies. Therefore, it seems unlikely that an altered endogenously produced insulin induced the generation of autoantibodies to insulin in this syndrome.
The usage of drugs containing SH-group may be potentially implicated in the pathogenesis of the syndrome. However, the retention time on HPLC of standard human insulin treated with SH-drugs and the binding activity of such insulin to its receptor were not altered significantly.
Until now, 26 patients with this syndrome were analyzed for HLA types. In these patients, each HLA - A11, Bw 62 (Bl5), Cw4 and DR4 was highly prevalent compared with that in the general population in Japan. Therefore, this result suggests that some subjects with genetically determined susceptibility are prone to the development of this syndrome.
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