Background and Aim:  The pathogenesis of hepatitis C virus (HCV)‐associated glucose intolerance remains unclear. Glucagon‐like peptide‐1 (GLP‐1), a gut hormone, synthesizes hepatic glycogen and is inactivated by dipeptidyl peptidase IV (DPPIV). The aims of this study were to investigate the alterations in the expression of GLP‐1 and DPPIV in HCV‐associated glucose intolerance.

Methods:  We enrolled patients with HCV‐ or hepatitis B virus (HBV)‐related liver disease (n = 94 and 37, respectively), patients with inflammatory bowel disease (IBD; n = 14) as disease controls, and healthy controls (n = 48). The serum or tissue GLP‐1 and DPPIV expression levels were determined by enzyme immunoassay, immunoblotting, or immunostaining. The hepatic glycogen content was assayed by periodic acid–Schiff staining.

Results:  The serum GLP‐1 levels were significantly decreased in the HCV group (4.9 ± 0.3 ng/mL) than those in the controls (7.5 ± 0.6 ng/mL), the HBV group (7.0 ± 0.5 ng/mL), or the IBD group (10.8 ± 1.0 ng/mL, P < 0.01). Although the ileum GLP‐1 expression was not significantly different between the controls and the HCV group, the DPPIV expression was significantly increased in the ileum, liver, and serum in the HCV group. Hepatic glycogen content was decreased to a greater extent in the HCV group than that in the HBV group (127.5 ± 5.3 vs 187.7 ± 6.6 arbitrary units; n = 19, P < 0.01).

Conclusion:  We demonstrated the altered expressions of GLP‐1 and DPPIV in patients with HCV‐associated glucose intolerance. Since hepatic glycogen synthesis, a GLP‐1 action, was impaired, the altered expressions of GLP‐1 and DPPIV may be involved in the development of HCV‐associated glucose intolerance.