Song Eun-Kyung, Hur Hyeon, Han Myung-Kwan
Department of Microbiology & Immunology, Chonbuk national University Medical School, Chonju 560-756, Korea.
Arch Pharm Res. 2003 Jul;26(7):559-63. doi: 10.1007/BF02976881.
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.
浸润胰岛的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β细胞破坏的重要介质。在非胰岛素依赖型糖尿病中，细胞因子也与高糖条件下β细胞功能受损有关。通过筛选各种阻断β细胞破坏的天然产物，我们最近发现表没食子儿茶素没食子酸酯（EGCG）可以预防细胞因子诱导的胰岛素瘤细胞系RINm5F细胞的体外破坏。在该研究中，我们认为EGCG可以通过抑制NF-κB激活下调一氧化氮合酶（NOS），从而预防细胞因子诱导的β细胞破坏。在此，为了验证EGCG的体内抗糖尿病作用，我们研究了EGCG是否也能预防多次低剂量链脲佐菌素（MLD-STZ）治疗诱导的实验性自身免疫性糖尿病，MLD-STZ被认为是I型自身免疫性糖尿病的诱导剂。在糖尿病诱导期给予EGCG（100mg/天/千克，共10天）可降低MLD-STZ引起的血糖水平升高。对β胰岛的体外分析表明，EGCG下调了MLD-STZ诱导的诱导型NOS（iNOS）表达。此外，形态学检查显示，EGCG治疗改善了MLD-STZ诱导的胰岛质量下降。综合这些结果表明，EGCG可以通过保护胰岛预防MLD-STZ诱导的糖尿病发病。因此，我们的结果揭示了EGCG在预防糖尿病进展方面可能的治疗价值。
