Dipeptidylpeptidase 4
Dipeptidyl peptidase 4 (DPP-4), also known as adenosine deaminase complexing protein 2 or CD26, is a protein that in humans is encoded by the DPP4 gene. DPP-4 is a serine exopeptidase that plays a major role in glucose metabolism. It is involved in the inactivation of incretin hormones, which are involved in the physiological regulation of glucose homeostasis. By cleaving incretins such as GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide), DPP-4 reduces their ability to stimulate insulin secretion in response to elevated blood glucose levels.
Function[edit | edit source]
DPP-4 is found on the surface of many cell types and has a broad range of substrates besides incretins. It is involved in immune regulation, signal transduction, and apoptosis. The enzyme's role in glucose metabolism has made it a target for the treatment of Type 2 diabetes. DPP-4 inhibitors, a class of oral hypoglycemics, work by blocking the action of DPP-4, thereby increasing the levels of active incretins. This leads to improved control of blood glucose levels.
Structure[edit | edit source]
The DPP-4 protein is a type II transmembrane glycoprotein composed of 766 amino acids. It has a large extracellular domain, a single transmembrane region, and a small intracellular tail. The extracellular domain contains the active site of the enzyme, which is responsible for its peptidase activity.
Clinical Significance[edit | edit source]
In the context of diabetes mellitus, the inhibition of DPP-4 has therapeutic implications. DPP-4 inhibitors, such as sitagliptin, vildagliptin, and saxagliptin, are used in the management of Type 2 diabetes to enhance incretin action, which in turn increases insulin secretion and decreases glucagon secretion. These effects are glucose-dependent, thereby reducing the risk of hypoglycemia.
DPP-4 has also been implicated in the pathogenesis of some cancers and immune disorders, making it a potential target for new therapeutic strategies beyond diabetes treatment.
See Also[edit | edit source]
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