ABSTRACT
The association between chronic HCV infection and type 2 diabetes mellitus (T2DM) has been established; however, there is limited research on ß-cell function particularly in the pre-diabetic population. Here, we evaluated indices of ß-cell function and insulin sensitivity across the spectrum from normal glucose tolerance to T2DM in individuals with and without chronic hepatitis C (CHC), and the effects of antiviral treatments on these variables. A total of 153 non-cirrhotic, non-fibrotic CHC patients with a BMI < 25 were enrolled in the study. Among them, 119 were successfully treated with either direct acting antiviral (DAA) drugs or pegylated interferon/ribavirin (IFN/RBV) anti-HCV therapy. Fasting state- and oral glucose tolerance test (OGTT)-derived indexes were used to evaluate ß-cell function and insulin sensitivity. Among all subjects, 19 (13%) had T2DM and 21% exhibited pre-diabetes including 8% isolated impaired fasting glucose (IFG) and 13% combined IFG and impaired glucose tolerance (IGT). Early and total insulin secretion adjusted for the degree of insulin resistance were decreased in prediabetic CHC patients compared to HCV-uninfected individuals. Viral eradication through DAA or IFN/RBV therapy demonstrated positive impacts on insulin sensitivity and ß-cell function in CHC patients who achieved sustained virologic response (SVR), regardless of fasting or OGTT state. These findings emphasize the role of HCV in the development of ß-cell dysfunction, while also suggesting that viral eradication can improve insulin secretion, reverse insulin resistance, and ameliorates glycemic control. These results have important implications for managing prediabetic CHC patients and could prevent diabetes-related clinical manifestations and complications.
ABSTRACT
As a novel class of noncoding RNAs, circular RNAs (circRNAs) have been recently reported to be involved in cell development and function. However, the functional role of circRNAs in hepatocellular carcinoma (HCC) remains unclear. In the present study, we found that the expression of human circ_101141 was upregulated in HCC tissues and cells. In addition, downregulation of circ_101141 dramatically inhibited cell proliferation, migration, and invasion in HCC cells. In addition, by using the bioinformatics tools, the potential target of circ_101141 was predicted. Mechanistic investigations indicated that circ_101141 acted as a miR-1297 "sponge"; meanwhile, Rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) was a direct target of miR-1297. Further experiments demonstrated that circ_101141 contributed to the progression of HCC by acting as competing endogenous RNA (ceRNA) of miR-1297 to regulate ROCK1 expression. Furthermore, knockdown of circ_101141 attenuated HCC tumorigenesis in vivo. Taken together, these findings indicated that circRNA circ_101141 acted as a ceRNA to facilitate tumorigenesis of HCC by regulating miR-1297/ROCK1 pathway.
