流行病学和实验性研究表明HCV感染与2型糖尿病相关。胰腺beta细胞受损是2型糖尿病进展的关键因素。我们利用病毒感染体系，研究HCV感染对胰岛瘤细胞株(MIN6)的影响。我们的研究表明HCV本身可起到剂量-时间依赖的致细胞病变作用。HCV感染抑制细胞增殖，并致使MIN6细胞株发生凋亡样死亡，包括细胞表面磷脂酰丝氨酸暴露、线粒体膜电位减小、caspase 3和多聚（ADP-核糖）聚合酶的活化以及细胞核DNA降解。然而，HCV感染细胞显示其具有完整核质及核膜的肿大的、低密度的细胞核，这又表明了异常的细胞凋亡样死亡。HCV也导致了内质网应激，并且可在MIN6细胞中检测到HCV RNA复制，尽管其感染力很高并且无子代病毒颗粒产生。综上，我们的资料表明，HCV感染通过涉及ER应激，依赖caspase3的特殊通路导致了胰腺beta细胞死亡。

吉林大学第一医院肝胆胰内科 李银萍 牛俊奇 摘译

本文首次发表于[PLoS ONE, 2012, 7（6）: e38522] 

Hepatitis C Virus Induced a Novel Apoptosis-Like Death of Pancreatic Beta Cells through a Caspase 3-Dependent Pathway 

   Epidemiological and experimental studies have suggested that Hepatitis C virus (HCV) infection is associated with the development of type 2 diabetes.Pancreatic beta cell failure is central to the progression of type 2 diabetes. Using virus infection system, we investigate the influence of HCV infection on the fate of the insulinoma cell line, MIN6. Our experiments demonstrate that the HCV virion itself is indispensable and has a dose- and time-dependent cytopathic effect on the cells. HCV infection inhibits cell proliferation and induces death of MIN6 cells with apoptotic characteristics, including cell surface exposure of phosphatidylserine, decreased mitochondrial membrane potential, activation of caspase 3 and poly(ADP-ribose) polymerase, and DNA fragmentation in the nucleus. However, the fact that HCV-infected cells exhibit a dilated,low-density nucleus with intact plasma and nuclear membrane indicates that a novel apoptosis-like death occurs. HCV infection also causes endoplasmic reticulum (ER) stress. Further, HCV RNA replication was detected in MIN6 cells, although the infection efficiency is very low and no progeny virus particle generates. Taken together, our data suggest that HCV infection induces death of pancreatic beta cells through an ER stress-involved, caspase 3-dependent, special pathway.点击下载此文件