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BioMed Research International
Volume 2014 (2014), Article ID 368703, 10 pages
http://dx.doi.org/10.1155/2014/368703
Review Article

The Nonglycemic Actions of Dipeptidyl Peptidase-4 Inhibitors

1Hanbang Body-Fluid Research Center and College of Oriental Medicine, Wonkwang University, 460 Iksandae-ro, Iksan 570-749, Republic of Korea
2Department of Internal Medicine, Wonkwang University School of Medicine & Hospital, 895 Muwang-ro, Iksan 570-711, Republic of Korea

Received 20 June 2014; Accepted 10 July 2014; Published 21 July 2014

Academic Editor: Dae Gill Kang

Copyright © 2014 Na-Hyung Kim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A cell surface serine protease, dipeptidyl peptidase 4 (DPP-4), cleaves dipeptide from peptides containing proline or alanine in the N-terminal penultimate position. Two important incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), enhance meal-stimulated insulin secretion from pancreatic β-cells, but are inactivated by DPP-4. Diabetes and hyperglycemia increase the DPP-4 protein level and enzymatic activity in blood and tissues. In addition, multiple other functions of DPP-4 suggest that DPP-4 inhibitor, a new class of antidiabetic agents, may have pleiotropic effects. Studies have shown that DPP-4 itself is involved in the inflammatory signaling pathway, the stimulation of vascular smooth cell proliferation, and the stimulation of oxidative stress in various cells. DPP-4 inhibitor ameliorates these pathophysiologic processes and has been shown to have cardiovascular protective effects in both in vitro and in vivo experiments. However, in recent randomized clinical trials, DPP-4 inhibitor therapy in high risk patients with type 2 diabetes did not show cardiovascular protective effects. Some concerns on the actions of DPP-4 inhibitor include sympathetic activation and neuropeptide Y-mediated vascular responses. Further studies are required to fully characterize the cardiovascular effects of DPP-4 inhibitor.