Dipeptidyl peptidase-4 (DPP4 or DPPIV), also known as adenosine deaminase complexing protein 2 or CD26 (cluster of differentiation 26) is a protein that, in humans, is encoded by the DPP4 gene. [5] DPP4 is related to FAP, DPP8, and DPP9. The enzyme was discovered in 1966 by Hopsu-Havu and Glenner, [6] and as a result of various studies on chemism, was called dipeptidyl peptidase IV [DP IV].
The protein encoded by the DPP4 gene is an enzyme expressed on the surface of most cell types and is associated with immune regulation, signal transduction, and apoptosis. It is a type II transmembrane glycoprotein, but a soluble form, which lacks the intracellular and transmembrane part, is present in blood plasma and various body fluids. DPP-4 is a serine exopeptidase that cleaves X-proline or X-alanine dipeptides from the N-terminus of polypeptides. Peptide bonds involving the cyclic amino acid proline cannot be cleaved by the majority of proteases and an N-terminal X-proline "shields" various biopeptides. [7] Extracellular proline-specific proteases therefore play an important role in the regulation of these biopeptides.
DPP-4 is known to cleave a broad range of substrates including growth factors, chemokines, neuropeptides, and vasoactive peptides. [8] [9] The cleaved substrates lose their biological activity in the majority of cases, but in the case of the chemokine RANTES and neuropeptide Y, DPP-4 mediated cleavage leads to a shift in the receptor subtype binding. [8]
DPP4 plays a major role in glucose metabolism. It is responsible for the degradation of incretins such as GLP-1. [10] Furthermore, it appears to work as a suppressor in the development of some tumors. [11] [12] [13] [14]
DPP-4 also binds the enzyme adenosine deaminase specifically and with high affinity. The significance of this interaction has yet to be established.
Animal studies suggest its pathogenetic role in development of fibrosis of various organs, such as liver and kidney. [15] [16]
CD26/DPPIV plays an important role in tumor biology, and is useful as a marker for various cancers, with its levels either on the cell surface or in the serum increased in some neoplasms and decreased in others. [17]
A class of oral hypoglycemics called dipeptidyl peptidase-4 inhibitors works by inhibiting the action of this enzyme, thereby prolonging incretin effect in vivo. [18]
Middle East respiratory syndrome coronavirus has been found to bind to DPP4. It is found on the surface of cells in the airways (such as the lungs) and kidneys. Scientists may be able to use this to their advantage by blocking the virus's entry into the cell. [19]
DPP4, [20] or its Mycobacterial homologue MtDPP, [21] might play a role in the pathogenesis of tuberculosis via cleavage of the chemokine C-X-C motif chemokine ligand 10 (CXCL10).
Vildagliptin, sold under the brand name Galvus and others, is an oral anti-hyperglycemic agent of the dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. Vildagliptin inhibits the inactivation of GLP-1 and GIP by DPP-4, allowing GLP-1 and GIP to potentiate the secretion of insulin in the beta cells and suppress glucagon release by the alpha cells of the islets of Langerhans in the pancreas.
Inhibitors of dipeptidyl peptidase 4 are a class of oral hypoglycemics that block the enzyme dipeptidyl peptidase-4 (DPP-4). They can be used to treat diabetes mellitus type 2.
Saxagliptin, sold under the brand name Onglyza, is an oral hypoglycemic of the dipeptidyl peptidase-4 (DPP-4) inhibitor class. Early development was solely by Bristol-Myers Squibb; in 2007 AstraZeneca joined with Bristol-Myers Squibb to co-develop the final compound and collaborate on the marketing of the drug.
C-C motif chemokine 22 is a protein that in humans is encoded by the CCL22 gene.
Prolyl endopeptidase (PE) also known as prolyl oligopeptidase or post-proline cleaving enzyme is an enzyme that in humans is encoded by the PREP gene.
Fibroblast activation protein alpha (FAP-alpha) also known as prolyl endopeptidase FAP is an enzyme that in humans is encoded by the FAP gene.
Dipeptidyl-peptidase 3 is an enzyme that in humans is encoded by the DPP3 gene.
Attractin is a protein that in humans is encoded by the ATRN gene.
Dipeptidyl-peptidase 2 is an enzyme that in humans is encoded by the DPP7 gene.
Dipeptidyl peptidase 8 is an enzyme that in humans is encoded by the DPP8 gene.
Xaa-Pro aminopeptidase 1 is an enzyme that in humans is encoded by the XPNPEP1 gene.
Dipeptidyl peptidase 9 is an enzyme that in humans is encoded by the DPP9 gene.
Dipeptidyl peptidase-4 inhibitors are enzyme inhibitors that inhibit the enzyme dipeptidyl peptidase-4 (DPP-4). They are used in the treatment of type 2 diabetes mellitus. Inhibition of the DPP-4 enzyme prolongs and enhances the activity of incretins that play an important role in insulin secretion and blood glucose control regulation. Type 2 diabetes mellitus is a chronic metabolic disease that results from inability of the β-cells in the pancreas to secrete sufficient amounts of insulin to meet the body's needs. Insulin resistance and increased hepatic glucose production can also play a role by increasing the body's demand for insulin. Current treatments, other than insulin supplementation, are sometimes not sufficient to achieve control and may cause undesirable side effects, such as weight gain and hypoglycemia. In recent years, new drugs have been developed, based on continuing research into the mechanism of insulin production and regulation of the metabolism of sugar in the body. The enzyme DPP-4 has been found to play a significant role.
Prolyl aminopeptidase is an enzyme. This enzyme catalyses the following chemical reaction
Xaa-Pro dipeptidyl-peptidase (EC 3.4.14.11, X-prolyl dipeptidyl aminopeptidase, PepX, X-prolyl dipeptidyl peptidase is an enzyme. It catalyses the following chemical reaction
Xaa-Xaa-Pro tripeptidyl-peptidase is an enzyme. It catalyses the following chemical reaction
Daniel Joshua Drucker is a Canadian endocrinologist. A Fellow of the Royal Society, he is a professor of medicine at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto. He is known for his research into intestinal hormones and their use in the treatment of diabetes, obesity, and other metabolic diseases, as well as intestinal failure.
Trelagliptin is a pharmaceutical drug used for the treatment of type 2 diabetes.
Omarigliptin (MK-3102) is a potent, long-acting oral antidiabetic drug of the DPP-4 inhibitor class used for once-weekly treatment of type 2 diabetes and currently under development by Merck & Co. It inhibits DPP-4 to increase incretin levels, which inhibit glucagon release, which in turn increases insulin secretion, decreases gastric emptying and decreases blood glucose levels.
Evogliptin is an antidiabetic drug in the dipeptidyl peptidase-4 (DPP-4) inhibitor or "gliptin" class of drugs. It was developed by the South Korean pharmaceutical company Dong-A ST and is approved for use in South Korea and Russia. In a meta-analysis involving data from 6 randomized controlled trials, Dutta et. al. demonstrated the good glycaemic efficacy and safety of this medicine as compared to other DPP4 inhibitors like sitagliptin and linagliptin.
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