Geniposide protects pancreatic INS‐1E β cells from hIAPP‐induced cell damage: Potential involvement of insulin degrading‐enzyme
Geniposide protects pancreatic INS‐1E β cells from hIAPP‐induced cell damage: Potential involvement of insulin degrading‐enzyme
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DOI：
10.1002/cbin.10394
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发表时间：
2015-04
影响因子：
3.9
通讯作者：
Yonglan Zhang;F. Yin;Jianhui Liu;Yanwen Wang
中科院分区：
文献类型：
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作者：
Yonglan Zhang;F. Yin;Jianhui Liu;Yanwen Wang
胰岛淀粉样蛋白沉积越来越被认为是2型糖尿病（T2DM）的一个致病特征，其沉积物含有独特的淀粉样蛋白生成肽胰岛淀粉样多肽（IAPP，也称为胰淀素）。IAPP的原纤维前体有助于其对胰腺β细胞的细胞毒性，并在引起2型糖尿病β细胞功能障碍中起重要作用。然而，本研究开发有效的抗IAPP毒性抑制剂一直极具挑战性。我们发现，用京尼平苷预孵卵可以剂量依赖性地阻止IAPP （hIAPP）诱导的INS - 1E细胞损伤，而杆菌肽（一种IDE活性抑制剂）可以显著地阻止京尼平苷对胰腺INS - 1E细胞的保护作用。京尼平苷诱导hIAPP的关键降解蛋白胰岛素降解酶（IDE）的表达，但对hIAPP的聚集无显著影响。这些发现表明，京尼平苷可以阻止hIAPP诱导的INS - 1E细胞毒性，包括IDE表达上调。
Islet amyloid deposition is increasingly seen as a pathogenic feature of type 2 diabetes mellitus (T2DM), with the deposits containing the unique amyloidogenic peptide islet amyloid polypeptide (IAPP, also known as amylin). The fibril precursors of IAPP contribute to its cytotoxicity on pancreatic β cells and be important in causing β‐cell dysfunction in T2DM. However, the development of effective this study, inhibitors against the toxicity of IAPP has been extremely challenging. We have found that pre‐incubation with geniposide dose‐dependently prevented human IAPP (hIAPP)‐induced cell damage in INS‐1E cells, and bacitracin, an inhibitor of IDE activity, prevented significantly the protective effects of geniposide in pancreatic INS‐1E cells significantly. Geniposide induced the expression of insulin‐degrading enzyme (IDE), a key degrading protein of hIAPP, but had no significant effect on the aggregation of hIAPP. These findings indicate that geniposide prevents hIAPP‐induced cytotoxicity in INS‐1E cells involving upregulation of IDE expression.