title: The nonglycemic actions of dipeptidyl peptidase-4 inhibitors.
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.
authors.affiliation: Hanbang Body-Fluid Research Center and College of Oriental Medicine, Wonkwang University, 460 Iksandae-ro, Iksan 570-749, Republic of Korea.
authors.forename: Na-Hyung
authors.initials: NH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Wonkwang University School of Medicine & Hospital, 895 Muwang-ro, Iksan 570-711, Republic of Korea.
authors.forename: Taeyang
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Internal Medicine, Wonkwang University School of Medicine & Hospital, 895 Muwang-ro, Iksan 570-711, Republic of Korea.
authors.forename: Dae Ho
authors.initials: DH
authors.lastname: Lee
mesh_terms: D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000473:pathology; D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4