Critical Role of Dipeptidyl Peptidase IV: A Therapeutic Target for Diabetes and Cancer

Abstract

Dipeptidyl Peptidase is one of the novel targets for antidiabetic and anticancer drugs. The dipeptidyl amminopeptidase IV, expressed in mammalian, releases X-Pro/Ala dipeptides from the N-terminus of peptides. It is responsible for the degradation of the incretin hormones which regulate blood glucose level. At present several DPP-IV inhibitors are approved for type-2 diabetes mellitus. These enzymes are also expressed in dimeric form on the surface of different cells (mature thymocytes, activated T cells, B cells, NK cells, macrophages, renal, prostate, liver and small intestinal epithelium, biliary canaliculae, and splenic sinus lining cells). Disruption of the local signaling environment is emerging as a major contributory factor in cancer development and significant modifier of the host's response. The focus of this review is on recent medicinal aspects of type-2 diabetes and cancer therapy as well as designing of DPP-IV inhibitors.

The perceptions of natural compounds against dipeptidyl peptidase 4 in diabetes: from in silico to in vivo

“…In fact, the roles of DPP-4 in tumorigenesis and progression, respectively, have been reviewed recently. 144,145 In lung cancer and pancreatic cancer, DPP-4 inhibitor can assuredly reduce cancer progression and promote the overall survival. 146 However, in breast cancer, prostate cancer, and endometrial carcinoma, DPP-4 inhibition would cause the opposite consequence which promotes cancer progression.…”

“…67,147,148 The role of DPP-4 inhibition in cancer treatment is inconclusive, but it is certain that DPP-4 inhibition in tumorigenesis and tumor development in site-specific tumor should be considered. 144,145 In addition to cancer development, opportunistic infection is another issue of DPP-4 inhibition. Anno et al reported a 69-year-old DM patient, who developed fever after taking vildagliptin for 1 week owing to hypercytokinemia.…”

Release of dipeptidyl peptidase IV inhibitory peptides from salmon (Salmosalar) skin collagen based on digestion–intestinal absorption invitro

“…DPP-IV is expressed in the liver, kidney, adrenal gland, intestine, placenta, spleen, lymphocytes and endothelial cells (Kshirsagar et al, 2011). This enzyme plays an important role in tumour invasion, inflammation regulation, cell migration, immune response, tissue remodelling, signal transduction and cell apoptosis (Yang et al, 2018;Davanso et al, 2019;De et al, 2019). Therefore, the regulation of DPP-IV may play a broad role in human health.…”

Inhibition of dipeptidyl peptidase IV by enzymatic hydrolysates derived from primary and secondary whey of fresh and Oaxaca cheeses

“…The treatment of type II diabetes is based on the use of synthetic oral hypoglycaemic agents, which sometimes produce adverse effects, including hypoglycaemic episodes and death (Camafort‐Babkowski, ). In this regard, researchers are searching for novel and natural drugs with potential inhibitory activity against dipeptidyl peptidase IV (DPP‐IV), a target for antidiabetic and anticancer drugs (Zúñiga‐Guajardo et al ; De et al ). DPP‐IV is a protease that inactivates incretin hormones, that is, glucose‐dependent insulin tropic polypeptide (GIP) and glucagon‐like peptide 1 (GLP‐1).…”

“…GIP and GLP‐1 are hormones involved in insulin secretion controlling pancreatic β‐cell proliferation and survival. Inhibition of DPP‐IV prolongs the activity of GIP and GLP‐1 maintaining glucose homeostasis (Green et al, ; De et al ). Currently, different inhibitory DPP‐IV peptides have been isolated from amaranth, wheat, soy, black bean, salmon, milk, whey, zein, lysozyme and porcine skin gelatin (Uchida et al ; Li‐Chan et al ; Velarde‐Salcedo et al ; Nongonierma and FitzGerald, ; De et al ), among others.…”