SUPPRESSION OF DIABETES IN NONOBESE DIABETIC MICE BY ORAL-ADMINISTRATION OF PORCINE INSULIN
SUPPRESSION OF DIABETES IN NONOBESE DIABETIC MICE BY ORAL-ADMINISTRATION OF PORCINE INSULIN
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DOI：
10.1073/pnas.88.22.10252
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发表时间：
1991-11-01
影响因子：
11.1
通讯作者：
WEINER, HL
中科院分区：
文献类型：
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作者：
ZHANG, ZJ;DAVIDSON, L;WEINER, HL
非肥胖型糖尿病（NOD）小鼠自发发展为与胰岛炎相关的自身免疫性糖尿病。已经研究了许多免疫调节疗法作为疾病过程的治疗。口服自身抗原髓鞘碱性蛋白和II型胶原抑制脑脊髓炎和关节炎的实验模型。我们现在已经发现，在NOD小鼠中，口服胰岛素延迟了糖尿病的发作，并在1年的时间内降低了糖尿病的发病率，在动物中，每周两次口服1 mg猪胰岛素，持续5周，然后每周一次，直到1岁。正如预期，口服胰岛素对血糖水平无代谢影响。口服胰岛素也可降低胰岛淋巴细胞浸润的严重程度。此外，来自口服胰岛素治疗的动物的脾T细胞过继转移对糖尿病的保护，表明口服胰岛素给药产生抑制疾病的活性细胞机制。这些结果表明，口服胰岛素影响NOD小鼠的糖尿病和胰腺细胞炎症过程，并提高了口服胰岛素或其他胰腺自身抗原可能为治疗自身免疫性糖尿病提供新方法的可能性。
Nonobese diabetic (NOD) mice spontaneously develop an autoimmune form of diabetes associated with insulitis. A number of immunomodulatory therapies have been investigated as a treatment for the disease process. Oral administration of the autoantigens myelin basic protein and collagen type II suppresses experimental models of encephalomyelitis and arthritis. We have now found that oral administration of insulin delays the onset and reduces the incidence of diabetes in NOD mice over a 1-year period in animals administered 1 mg of porcine insulin orally twice a week for 5 weeks and then weekly until 1 year of age. As expected, orally administered insulin had no metabolic effect on blood glucose levels. The severity of lymphocytic infiltration of pancreatic islets was also reduced by oral administration of insulin. Furthermore, splenic T cells from animals orally treated with insulin adoptively transfer protection against diabetes, demonstrating that oral insulin administration generates active cellular mechanisms that suppress disease. These results show that oral insulin affects diabetes and the pancreatic cellular inflammatory process in the NOD mouse and raise the possibility that oral administration of insulin or other pancreatic autoantigens may provide a new approach for the treatment of autoimmune diabetes.