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

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

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

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

• Incretin
• Glucagon-like peptide-1 receptor
• Type 2 diabetes
• Hypoglycemia