The Dipeptidyl Peptidase-4 (DPP-IV) enzyme plays a significant role in various bodily processes, including metabolism. Its widespread presence and diverse functions make it a subject of scientific interest. Understanding how DPP-IV operates provides insight into maintaining overall health and developing treatments for certain conditions.
What is the DPP-IV Enzyme?
The Dipeptidyl Peptidase-4 (DPP-IV) enzyme, also identified as CD26, is a serine protease. This means it uses a serine amino acid in its active site to break down other proteins. DPP-IV is found extensively throughout the human body, appearing on the surface of most cell types, including epithelial cells, endothelial cells, and various immune cells like T lymphocytes.
A soluble form of DPP-IV also circulates in the blood plasma and other bodily fluids. Its primary biological function involves cleaving dipeptides from the N-terminus of various polypeptides. This cleavage occurs specifically when proline or alanine is the second amino acid in the peptide chain. This enzymatic action can either inactivate the cleaved peptides or generate new bioactive molecules.
Its Role in Glucose Metabolism
The DPP-IV enzyme significantly impacts blood glucose regulation, especially in Type 2 Diabetes. It does this by controlling the activity of incretin hormones, primarily Glucagon-Like Peptide-1 (GLP-1) and Glucose-Dependent Insulinotropic Polypeptide (GIP). These incretins are released from the intestines in response to food intake and play a role in glucose homeostasis.
GLP-1 and GIP stimulate the pancreas to release insulin in a glucose-dependent manner, meaning insulin is secreted more when blood glucose levels are high. GLP-1 also helps suppress glucagon secretion from the alpha-cells of the pancreas, which further helps lower blood glucose. The DPP-IV enzyme rapidly inactivates these incretin hormones by cleaving them into inactive forms. This rapid breakdown limits the duration of their glucose-regulating effects.
In Type 2 Diabetes, the incretin effect (enhanced insulin secretion in response to oral glucose) is impaired. The rapid inactivation of GLP-1 and GIP by DPP-IV contributes to this impairment, leading to higher blood glucose levels after meals. Understanding this mechanism has directed efforts toward therapeutic interventions that target DPP-IV to improve glucose control.
DPP-IV Inhibitors and Their Therapeutic Use
The understanding of DPP-IV’s role in glucose metabolism led to the development of a class of medications known as DPP-IV inhibitors, often called ‘gliptins’. These oral medications are approved for managing Type 2 Diabetes in adults. Their mechanism involves blocking the DPP-IV enzyme, which prevents the rapid breakdown of naturally occurring incretin hormones like GLP-1 and GIP.
By inhibiting DPP-IV, these medications prolong the active life of incretin hormones in the body. This extended activity leads to increased glucose-dependent insulin secretion from pancreatic beta cells and reduced glucagon secretion from alpha cells, thereby improving blood glucose control. This approach helps lower both fasting and post-meal blood glucose levels, contributing to a reduction in average blood glucose over time, as measured by HbA1c.
Common examples of DPP-IV inhibitors include sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), and alogliptin (Nesina). These medications are well-tolerated and are preferred because they do not cause weight gain and carry a low risk of hypoglycemia (low blood glucose) when used alone. They can be used as a standalone treatment or in combination with other diabetes medications like metformin.
Beyond Glucose: Other Biological Functions
While its role in glucose metabolism is well-established, the DPP-IV enzyme participates in various other biological functions. It is involved in immune regulation, influencing the activity of different immune cells and modulating numerous cytokines, chemokines, and peptide hormones. This suggests a broader involvement in the body’s defense mechanisms and inflammatory responses.
DPP-IV has also been linked to cardiovascular health, with research exploring its potential effects on the heart, kidneys, and blood vessels. Studies have also investigated its connection to certain types of cancer, where its levels on cell surfaces or in serum may serve as markers. Although these roles are areas of ongoing research and are less understood compared to its metabolic function, they highlight the enzyme’s diverse impact on human physiology.