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

Abstract

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.

The Metabolic Regulator Histone Deacetylase 9 Contributes to Glucose Homeostasis Abnormality Induced by Hepatitis C Virus Infection

“…The HCV J399EM strain was derived from the JFH-1 virus by inserting enhanced green fluorescent protein into the HCV NS5A region (20). Virus production and infection were performed as described elsewhere (21 The transgenic C/O Tg mice harboring both the human CD81 and occludin (OCLN) genes were constructed as described previously (19). We used 8-to 12-week-old and sex-matched mice for in vivo experiments.…”

The Effect of Hepatitis C Virus Eradication with New Direct Acting Antivirals on Glucose Homeostasis in Non-Diabetic Egyptian Patients

“…The second assumption is direct inhibition of insulin secretion by HCV itself which improved after eradication. This assumption was proved before by several studies [21,22].…”

3-Hydroxykynurenic Acid and Type 2 Diabetes: Implications for Aging, Obesity, Depression, Parkinson’s Disease, and Schizophrenia

“…There was no correlation between KYNA and IR, probably because of downregulation of P5P-dependent KATs despite increased availability of KYN as a substrate for KYNA formation. The absence of KYNA correlations with HOMA-IR in our study of HCV subjects does not preclude possible KYNA involvement in the development of T2DM in non-HCV subjects because of additional impact of HCVinducible apoptosis-like death of pancreatic beta cells through a caspase 3-dependent pathway (Wang et al 2012 ).…”