DPP4 in diabetes

Abstract

Dipeptidyl-peptidase 4 (DPP4) is a glycoprotein of 110 kDa, which is ubiquitously expressed on the surface of a variety of cells. This exopeptidase selectively cleaves N-terminal dipeptides from a variety of substrates, including cytokines, growth factors, neuropeptides, and the incretin hormones. Expression of DPP4 is substantially dysregulated in a variety of disease states including inflammation, cancer, obesity, and diabetes. Since the incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide (GIP), are major regulators of post-prandial insulin secretion, inhibition of DPP4 by the gliptin family of drugs has gained considerable interest for the therapy of type 2 diabetic patients. In this review, we summarize the current knowledge on the DPP4–incretin axis and evaluate most recent findings on DPP4 inhibitors. Furthermore, DPP4 as a type II transmembrane protein is also known to be cleaved from the cell membrane involving different metalloproteases in a cell-type-specific manner. Circulating, soluble DPP4 has been identified as a new adipokine, which exerts both para- and endocrine effects. Recently, a novel receptor for soluble DPP4 has been identified, and data are accumulating that the adipokine-related effects of DPP4 may play an important role in the pathogenesis of cardiovascular disease. Importantly, circulating DPP4 is augmented in obese and type 2 diabetic subjects, and it may represent a molecular link between obesity and vascular dysfunction. A critical evaluation of the impact of circulating DPP4 is presented, and the potential role of DPP4 inhibition at this level is also discussed.

Liraglutide alters DPP4 in the circumvallate papillae of type 2 diabetic rats

“…In particular, DPP4, also known as CD26 (Kameoka et al 1993), is a cell-surface aminopeptidase with serine protease activity, belonging to the S9B family of serine proteases (Röhrborn et al 2015). It is expressed on the apical surfaces of epithelial and acinar cells and in endothelial cells, fibroblasts, and lymphocytes (Dinjens et al 1989, Mentzel et al 1996; however, DPP4 also exists as a soluble circulating form in plasma (Kikuchi et al 1988).…”

Wound Healing Process, Diabetes and Implications of Dipeptidyl Peptidase IV (DPP IV/CD26)

“…Due to the increased number of beta cells, the insulin concentration increased in pancreatic islets [27]. Likewise, sitagliptin showed increased proliferation of endothelial cells around and inside of the grafts.…”

“…For instance, the colocalization of DPP IV/CD26 with the chemotactic receptor CXCR4, which is a receptor for stromal cell-derived factor 1α (SDF-1α), influences CXCR4-signaling properties for attracting endothelial progenitor cells at the inflammatory site. SDF-1α locally produced in damaged and inflamed tissues promotes angiogenesis and has an important role in diabetes as a protector of stem-cell-derived insulin-producing cells from glucotoxicity and as a promotor of betacell survival in mice [14].…”

“…DPP IV/CD26 changes the ability of NPY to bind to its Y1 subtype of receptor and therefore terminates the action of NPY at the Y1 receptor, moderating thus the regulation of vascular smooth muscle contraction and angiogenesis [16]. Furthermore, an important role of NPY was noticed in pancreatic beta-cell survival as well as in glucose homeostasis, where NPY has the ability to suppress insulin secretion [14].…”

A Note Study on Antidiabetic Effect of Main Molecules Contained in Clove Using Molecular Modeling Interactions with DPP-4 Enzyme

“…Moreover, as a serine protease, DPP-4 cleaves numerous substrates, which further amplifies its complexity of action. Thus, DPP-4 is involved in signaling processes, immune cell activation, and its dysregulated expression and release is associated with numerous diseases [25].…”