Chronic hepatitis C virus infection impairs insulin secretion by regulation of p38δ MAPK-dependent exocytosis in pancreatic β-cells

Clin Sci (Lond). 2020 Mar 13;134(5):529-542. doi: 10.1042/CS20190900.


Chronic hepatitis C virus (HCV) infection has a close association with type 2 diabetes mellitus. Although the mechanisms of insulin resistance in chronic hepatitis C (CHC) patients have been extensively studied, little attention has been given to the role of β-cell function in HCV-associated diabetes. Here, we analysed β-cell function in CHC patients and HCV-infected mouse model and found in addition to insulin resistance, impaired pancreatic β-cell function occurred in CHC patients and HCV-infected C/OTg mice, not only in diabetic individuals but also in individuals with impaired fasting glucose levels. Both first-phase and second-phase insulin secretion were impaired, at least partially due to the reduction of exocytosis of secretory insulin-containing granules following HCV infection. Up-regulated p38δ in HCV-infected β-cells resulted in inactivation of protein kinase D (PKD), which was responsible for impaired insulin secretory capacity of β-cells. Thus, impaired insulin secretion due to HCV infection in β-cells contributes to HCV-associated type 2 diabetes. These findings provided a new inspiration for the important prognostic and therapeutic implications in the management of CHC patients with impaired fasting glucose.

Keywords: beta cell; diabetes; hcv; insulin secretion; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / metabolism
  • Exocytosis*
  • Glucose Intolerance / blood
  • Glucose Intolerance / metabolism
  • Glucose Intolerance / virology
  • Hepatitis C, Chronic / metabolism*
  • Hepatitis C, Chronic / virology
  • Humans
  • Insulin / metabolism
  • Insulin Secretion*
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / virology
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinase 13 / metabolism*
  • Protein Kinase C / metabolism


  • Insulin
  • Mitogen-Activated Protein Kinase 13
  • protein kinase D
  • Protein Kinase C