Stefano Balbo, Eleonora Barabesi (University of Turin, Medicine)
-Definition
Dipeptidyl peptidase-4 (DPP4), also known as adenosine deaminase complexing protein 2 or
CD26 is a protein that, in humans, is encoded by the
DPP4 gene.
This protein is a serine exopeptidase and complex enzyme that is expressed on the surface of most cell types.
-Molecular Structure
-Function
The protein encoded by the
DPP4 gene is an antigenic enzyme expressed on the surface of most cell types and is associated with immune regulation, signal transduction and apoptosis. It is an intrinsic membrane glycoprotein and a serine exopeptidase that cleaves X-proline dipeptides from the N-terminus of polypeptides.
It is a rather indiscriminate enzyme for which a diverse range of substrates are known. The substrates of
CD26/DPPIV are proline(or alanine)-containing peptides and include growth factors, chemokines, neuropeptides, and vasoactive peptides.
DPP4 is related to attractin,
FAP, DPP8 and
DPP9.
DPP4 plays a major role in glucose metabolism. It is responsible for the degradation of incretins such as
GLP-1. (Link:
Phisiology of incretin)
GLP-1
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GIP
|
Furthermore, it appears to work as a suppressor in the development of cancer and tumours
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.
DPP-4 also binds the enzyme adenosine deaminase specifically and with high affinity. The significance of this interaction has yet to be established.
-Role of DPP4 in Type 2 diabetes therapy
Diabetes mellitus type 2 is a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. (
Type 2 diabetes )
A new class of oral hypoglycemics called dipeptidyl peptidase-4 inhibitors work by inhibiting the action of this enzyme, thereby prolonging incretin effect in vivo. (
Inhibitors of DPP4 )
Sitagliptin
|
Vitagliptin
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Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) are enzyme inhibitors that inhibit the enzyme dipeptidyl peptidase-4 (DPP-4) and are a potent treatment for type 2 diabetes. 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.
Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes mellitus
DDP4 Inhibitors Type 2 Diabetes
link
External Links
- Cardiovascular effects of DPP-4 inhibition
- Long-term dipeptidyl-peptidase 4 inhibition
