Review
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World J Gastroenterol. Apr 21, 2013; 19(15): 2298-2306
Published online Apr 21, 2013. doi: 10.3748/wjg.v19.i15.2298
Dipeptidyl peptidase-4: A key player in chronic liver disease
Minoru Itou, Takumi Kawaguchi, Eitaro Taniguchi, Michio Sata
Minoru Itou, Eitaro Taniguchi, Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan
Takumi Kawaguchi, Michio Sata, Division of Gastroenterology, Department of Medicine and Department of Digestive Disease Information and Research, Kurume University School of Medicine, Kurume 830-0011, Japan
Author contributions: Itou M and Kawaguchi T collected the materials and wrote the manuscript; Taniguchi E discussed the topic; Sata M supervised the manuscript.
Correspondence to: Takumi Kawaguchi, MD, PhD, Division of Gastroenterology, Department of Medicine and Department of Digestive Disease Information and Research, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. takumi@med.kurume-u.ac.jp
Telephone: +81-942-317902 Fax: +81-942-317820
Received: October 29, 2012
Revised: February 27, 2013
Accepted: March 6, 2013
Published online: April 21, 2013
Abstract

Dipeptidyl peptidase-4 (DPP-4) is a membrane-associated peptidase, also known as CD26. DPP-4 has widespread organ distribution throughout the body and exerts pleiotropic effects via its peptidase activity. A representative target peptide is glucagon-like peptide-1, and inactivation of glucagon-like peptide-1 results in the development of glucose intolerance/diabetes mellitus and hepatic steatosis. In addition to its peptidase activity, DPP-4 is known to be associated with immune stimulation, binding to and degradation of extracellular matrix, resistance to anti-cancer agents, and lipid accumulation. The liver expresses DPP-4 to a high degree, and recent accumulating data suggest that DPP-4 is involved in the development of various chronic liver diseases such as hepatitis C virus infection, non-alcoholic fatty liver disease, and hepatocellular carcinoma. Furthermore, DPP-4 occurs in hepatic stem cells and plays a crucial role in hepatic regeneration. In this review, we described the tissue distribution and various biological effects of DPP-4. Then, we discussed the impact of DPP-4 in chronic liver disease and the possible therapeutic effects of a DPP-4 inhibitor.

Keywords: Incretin, Viral hepatitis, Insulin resistance, Steatohepatitis, Cancer, Sitagliptin, Vildagliptin, Alogliptin, Teneligliptin, Linagliptin

Core tip: Dipeptidyl peptidase-4 (DPP-4) is a membrane-associated peptidase, also known as CD26. DPP-4 has widespread organ distribution throughout the body and exerts pleiotropic effects via its peptidase activity. In this review, we described the tissue distribution and various biological effects of DPP-4. Then, we discussed the impact of DPP-4 in chronic liver disease and the possible therapeutic effects of a DPP-4 inhibitor.