Insulin enhances the peroxidase activity of heme by forming heme-insulin complex: Relevance to type 2 diabetes mellitus
Insulin enhances the peroxidase activity of heme by forming heme-insulin complex: Relevance to type 2 diabetes mellitus
复制标题
胰岛素通过形成血红素-胰岛素复合物增强血红素过氧化物酶活性：与 2 型糖尿病的相关性
DOI：
10.1016/j.ijbiomac.2017.04.113
复制
发表时间：
2017
影响因子：
8.2
通讯作者：
Li Hailing
中科院分区：
文献类型：
--
作者：
Huang Yi;Yang Zhen;Xu Huan;Zhang Pengfei;Gao Zhonghong;Li Hailing
Evidences have implicated the involvement of heme in the type 2 diabetes mellitus (T2Dm) pathogenesis, but possible mediators linking between heme and diabetes are still poorly understood. Here, we explored a potential mechanism that linked heme, insulin and diabetes. Our results demonstrated the formation of heme-insulin complex by two classical methods,i.e.UV–vis and capillary electrophoresis-frontal analysis (CE-FA). UV–vis results implied heme binding insulin via bis-histidine sites, and CE-FA further revealed that, when insulin uses two sites binding with heme, this interaction occurs at high affinity (Kd= 3.13 × 10−6M). Molecule docking supported that histidine-B5 of insulin binds with heme-Fe. In addition to that, tyrosine-B26, phenylalanine-B1 and valine-B2 are also contributed to binding heme. The binding amplified the peroxidase activity of heme itself. Under oxidative and nitrative stress, it affects pathogenesis of diabetes from two aspects: promoting insulin cross-linking that leads to permanent loss of insulin functionality on one hand, and enhancing protein tyrosine nitration that may result in inactivation of proteins associated with diabetes on the other hand. This study suggested that the enhanced peroxidase activity of heme through binding with insulin might be a previously unrecognized contributor to the pathogenesis of T2Dm in some heme-associated disorders.
