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Lipotoxicity has been implicated in pancreatic β-cell dysfunction in type 2 diabetes, but the exact mechanisms remain unknown. The current study explored the role of the endoplasmic reticulum (ER) stress pathway in cholesterol-induced lipotoxicity. Two different insulinoma cell lines were treated with cholesterol with or without inhibitors. ER stress-associated proteins glucose-regulated protein (GRP) 78, activating transcription factor (ATF) 4 and C/EBP homologous protein (CHOP), as was phosphorylation of eukaryotic initiation factor (EIF) 2α, were all up-regulated by cholesterol. Cholesterol also up-regulated microtubule-associated protein 1 light chain 3 (LC3)-II and stimulated the formation of autophagic vacuoles and LC3-II aggregates. Cholesterol-induced autophagy and cell injuries were suppressed by pretreatment with the ER stress inhibitor 4-phenylbutyrate (4-PBA). Pretreatment with autophagy inhibitors E-64d/pepstatin A increased ER stress-induced cell injuries as indicated by increased cell apoptosis and decreased insulin secretion. These results suggest that cholesterol treatment induces apoptosis and dysfunction of β-cells, and enhances autophagy through activation of the ER stress pathway. More importantly, autophagy induced by cholesterol may protect β-cells against ER stress-associated cell damages. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection greatly increases the risk of nephropathy. In this observational study, we aimed to explore the relationship between viral hepatitis infection and chronic kidney disease (CKD), identify risk factors, and determine the effect of antiviral treatment on CKD in Chinese patients with chronic HCV infection. A total of 2,435 study subjects were enrolled and divided into four groups: the HCV infection, HBV infection, HBV and HCV co-infection, and uninfected control groups. Of these, 207 patients with chronic hepatitis C (CHC) were given standard dual therapy [subcutaneous injection of recombinant interferon (IFN)-α2b and oral ribavirin (RBV)] for 48 weeks. We found that the prevalence of CKD gradually increased with age in all groups and was significantly increased in patients 60 years or older. Multivariate logistic regression analyses showed that persistent HCV infection was significantly associated with CKD [odds ratio (OR), 1.33; 95% confidence interval (CI), 1.06-1.66; P = 0.013], whereas there was no significant link between CKD and spontaneous HCV clearance (OR, 1.23; 95% CI, 0.79-1.90; P = 0.364), HBV infection (OR, 0.73; 95% CI, 0.44-1.19; P = 0.201), or HBV/HCV co-infection (OR, 1.40; 95% CI, 0.81-2.40; P = 0.234). Notably, after anti-HCV therapy, the serum creatinine concentration was significantly decreased (76.0, 75.5-79.4 μmol/L) from the pretreatment level (95.0, 93.0-97.2 μmol/L), both in patients who showed an end of treatment virological response (ETVR) and those who did not (P < 0.001). Also, in both the ETVR and non-ETVR groups, the percentages of patients with an estimated glomerular filtration rate (eGFR) ≥90 ml/min/1.73 m2 increased significantly (P < 0.001), whereas the percentages of those with an eGFR <60 ml/min/1.73 m2 significantly decreased (P < 0.001). In conclusion, persistent HCV infection was independently associated with CKD, and antiviral treatment with IFN plus RBV can improve renal function and reverse CKD in HCV-infected patients. [ABSTRACT FROM AUTHOR]