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World J Gastroenterol. 2013 Apr 21;19(15):2298-306. doi: 10.3748/wjg.v19.i15.2298.

Dipeptidyl peptidase-4: a key player in chronic liver disease.

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Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan.


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.


Alogliptin; Cancer; Incretin; Insulin resistance; Linagliptin; Sitagliptin; Steatohepatitis; Teneligliptin; Vildagliptin; Viral hepatitis

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