title: Dipeptidyl peptidase-4: a key player in chronic liver disease.
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.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Itou
authors.forename: Takumi
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Eitaro
authors.initials: E
authors.lastname: Taniguchi
authors.forename: Michio
authors.initials: M
authors.lastname: Sata
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000502:physiology*; D058625:End Stage Liver Disease / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006526:Hepatitis C / Q000378:metabolism*; D006801:Humans; D054795:Incretins / Q000627:therapeutic use; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease
chemical_list: D054795:Incretins; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
keywords: Alogliptin; Cancer; Incretin; Insulin resistance; Linagliptin; Sitagliptin; Steatohepatitis; Teneligliptin; Vildagliptin; Viral hepatitis