DPPIV

DPPIV, also known as dipeptidyl peptidase IV, is an enzyme that plays a significant role in metabolic regulation. It is a serine protease found on the surface of many cell types, including those in the intestines, liver, pancreas, and immune cells. The primary function of DPPIV is to cleave dipeptides from the N-terminus of peptides and proteins.

A key substrate for DPPIV is glucagon-like peptide-1 (GLP-1), an incretin hormone that is released after eating. GLP-1 stimulates insulin secretion from the pancreas and inhibits glucagon release, thereby lowering blood glucose levels. DPPIV rapidly inactivates GLP-1, limiting its duration of action. This inactivation mechanism is crucial for preventing excessive insulin release and hypoglycemia.

In addition to GLP-1, DPPIV degrades other biologically active peptides, such as glucose-dependent insulinotropic polypeptide (GIP), also an incretin hormone, and various chemokines involved in immune responses. Its broad substrate specificity suggests a diverse range of physiological roles beyond glucose homeostasis.

Due to its role in GLP-1 inactivation, DPPIV has become a therapeutic target. DPP-IV inhibitors are a class of oral medications used to treat type 2 diabetes. By blocking the activity of DPPIV, these drugs prolong the action of GLP-1, leading to improved glycemic control. These inhibitors are generally well-tolerated and have a low risk of hypoglycemia when used as monotherapy. Research continues to explore other potential therapeutic applications for modulating DPPIV activity in various disease states.