Epigallocatechin gallate prevents autoimmune diabetes induced by multiple low doses of streptozotocin in mice
Epigallocatechin gallate prevents autoimmune diabetes induced by multiple low doses of streptozotocin in mice
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DOI：
10.1007/bf02976881
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发表时间：
2003-07-01
影响因子：
6.7
通讯作者：
Han, MK
中科院分区：
文献类型：
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作者：
Song, EK;Hur, H;Han, MK
胰岛免疫细胞产生的细胞因子被认为是胰岛素依赖型糖尿病中破坏胰岛β细胞的重要介质。在非胰岛素依赖型糖尿病中，细胞因子也与高糖条件下的胰岛细胞功能受损有关。通过对各种阻断β细胞破坏的天然产物的筛选，我们最近发现表没食子儿茶素没食子酸酯(EGCG)可以防止细胞因子诱导的胰岛素瘤细胞系RINm5F细胞的体外破坏。在这项研究中，我们认为EGCG可能通过抑制核因子-kappaB的激活而下调一氧化氮合酶(NOS)，从而防止细胞因子诱导的β细胞破坏。在此，为了验证EGCG的体内抗糖尿病作用，我们检测了EGCG还可以预防多次小剂量链脲佐菌素(MLD-STZ)治疗的实验性自身免疫性糖尿病的可能性，MLD-STZ被认为是I型自身免疫性糖尿病的诱因。在MLD-STZ诱导糖尿病期间给予EGCG(100 mg/天/kg，连续10天)可降低MLD-STZ引起的血糖水平的升高。体外胰岛分析显示，EGCG下调MLD-STZ诱导的诱导型一氧化氮合酶(INOS)的表达。此外，形态学检查显示，EGCG治疗改善了MLD-STZ所致的胰岛质量减少。综上所述，这些结果表明EGCG可以通过保护胰岛来预防MLD-STZ诱导的糖尿病的发生。因此，我们的结果揭示了EGCG预防糖尿病进展的可能治疗价值。
Cytokines produced by immune cells infiltrating pancreatic islets have been incriminated as important mediators of beta-cell destruction in insulin-dependent diabetes mellitus. In non insulin-dependent diabetes, cytokines are also associated with impaired beta-cell function in high glucose condition. By the screening of various natural products blocking beta-cell destruction, we have recently found that epigallocatechin gallate (EGCG) can prevent the in vitro destruction of RINm5F cell, an insulinoma cell line, that is induced by cytokines. In that study we suggested that EGCG could prevent cytokine-induced beta-cell destruction by down-regulation of nitric oxide synthase (NOS) through inhibition of NF-kappaB activation. Here, to verify the in vivo antidiabetogenic effect of EGCG, we examined the possibility that EGCG could also prevent the experimental autoimmune diabetes induced by the treatment of multiple low doses of streptozotocin (MLD-STZ), which is recognized as an inducer of type I autoimmune diabetes. Administration of EGCG (100 mg/day/kg for 10 days) during the MLD-STZ induction of diabetes reduced the increase of blood glucose levels caused by MLD-STZ. Ex vivo analysis of beta-islets showed that EGCG downregulates the MLD-STZ-induced expression of inducible NOS (iNOS). In addition, morphological examination showed that EGCG treatment ameliorated the decrease of islet mass induced by MLD-STZ. In combination these results suggest that EGCG could prevent the onset of MLD-STZ-induced diabetes by protecting pancreatic islets. Our results therefore revealed the possible therapeutic value of EGCG for the prevention of diabetes mellitus progression.