Beta cell expression of IGF-I leads to recovery from type 1 diabetes.
Beta cell expression of IGF-I leads to recovery from type 1 diabetes.
复制标题
β 细胞表达 IGF-I 可促进 1 型糖尿病康复。
DOI：
--
复制
发表时间：
2002
影响因子：
15.9
通讯作者：
F. Bosch
中科院分区：
文献类型：
--
作者：
M. George;E. Ayuso;A. Casellas;C. Costa;J. Devedjian;F. Bosch
1 型糖尿病患者在疾病发作后即 β 细胞破坏几乎完全时被识别出来。胰岛细胞前体的β细胞再生可能会逆转这种疾病，但可以诱导β细胞新生和复制并防止新一轮自身免疫破坏的因素仍有待确定。在这里，我们表明，在多次低剂量链脲佐菌素 (STZ) 治疗后，转基因小鼠（C57BL/6-SJL 和 CD-1 遗传背景）β 细胞中 IGF-I 的表达可以抵消细胞毒性和胰岛素炎。 STZ治疗的非转基因小鼠出现高血糖和低胰岛素血症、体重减轻并死亡。相比之下，STZ治疗的C57BL/6-SJL转基因小鼠在大约1个月内表现出轻度高血糖，此后它们使血糖正常化并存活下来。 STZ治疗后，所有CD-1小鼠均出现高血糖、低胰岛素血症、多饮和多食。然而，STZ 治疗的 CD-1 转基因小鼠逐渐使所有代谢参数正常化并存活下来。由于新生和β细胞复制，β细胞质量同时增加。因此，我们的结果表明，β细胞中IGF-I的局部表达可以再生胰岛并抵抗1型糖尿病，这表明IGF-I基因转移到胰腺可能是治疗这种疾病的合适疗法。
Patients with type 1 diabetes are identified after the onset of the disease, when beta cell destruction is almost complete. beta cell regeneration from islet cell precursors might reverse this disease, but factors that can induce beta cell neogenesis and replication and prevent a new round of autoimmune destruction remain to be identified. Here we show that expression of IGF-I in beta cells of transgenic mice (in both C57BL/6-SJL and CD-1 genetic backgrounds) counteracts cytotoxicity and insulitis after treatment with multiple low doses of streptozotocin (STZ). STZ-treated nontransgenic mice developed high hyperglycemia and hypoinsulinemia, lost body weight, and died. In contrast, STZ-treated C57BL/6-SJL transgenic mice showed mild hyperglycemia for about 1 month, after which they normalized glycemia and survived. After STZ treatment, all CD-1 mice developed high hyperglycemia, hypoinsulinemia, polydipsia, and polyphagia. However, STZ-treated CD-1 transgenic mice gradually normalized all metabolic parameters and survived. beta cell mass increased in parallel as a result of neogenesis and beta cell replication. Thus, our results indicate that local expression of IGF-I in beta cells regenerates pancreatic islets and counteracts type 1 diabetes, suggesting that IGF-I gene transfer to the pancreas might be a suitable therapy for this disease.