Dipeptidyl peptidase-4, often shortened to DDP4, is an enzyme found throughout the human body. Enzymes are specialized proteins that act as catalysts, speeding up specific chemical reactions within cells and tissues. DDP4 plays a part in various biological processes, influencing how the body functions.
Understanding DDP4
DDP4’s primary biological function involves breaking down certain peptide hormones by cleaving off specific amino acid pairs from their N-terminus. It specifically targets peptides with proline or alanine as the second-to-last amino acid. A significant group of these targets are incretin hormones, particularly glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).
Incretin hormones are released from the gut into the bloodstream shortly after a person eats. Their role is to signal the pancreas to release insulin in a glucose-dependent manner, meaning insulin is released when blood sugar levels are high. They also help to suppress the secretion of glucagon, a hormone that raises blood sugar. DDP4 rapidly inactivates these incretins. This enzyme is present in various tissues, including the gut, kidneys, and immune cells, and can also circulate in the blood as a soluble form.
DDP4’s Role in Diabetes
DDP4’s activity directly impacts blood sugar regulation in type 2 diabetes. In type 2 diabetes, the body struggles to produce or effectively use insulin, leading to elevated blood glucose levels. The rapid breakdown of incretin hormones by DDP4 can worsen this issue.
This limitation of incretin activity contributes to the difficulty in controlling blood sugar in individuals with type 2 diabetes. Managing DDP4 activity presents a strategy to enhance the body’s natural mechanisms for lowering blood glucose by prolonging the action of incretins, thereby supporting better glycemic control.
DDP4 Inhibitor Medications
A class of medications known as DDP4 inhibitors, or “gliptins,” was developed to help manage type 2 diabetes. These oral medications work by blocking the enzymatic action of DDP4, which prevents the rapid degradation of incretin hormones like GLP-1 and GIP, allowing them to remain active in the bloodstream for a longer duration.
The prolonged activity of incretins leads to several beneficial effects for individuals with type 2 diabetes. It enhances glucose-dependent insulin secretion from pancreatic beta-cells. These medications also decrease glucagon secretion from pancreatic alpha-cells and can reduce glucose production by the liver.
Common examples of these medications include sitagliptin, saxagliptin, linagliptin, and vildagliptin, which are typically taken once daily. DDP4 inhibitors are generally well-tolerated, have a neutral effect on body weight, and carry a low risk of hypoglycemia when used alone. They have been shown to reduce HbA1c levels, a measure of average blood sugar over several months, by approximately 0.4% to 0.9%.
Beyond Glucose Regulation
While DDP4 is known for its role in glucose metabolism, its functions extend beyond blood sugar regulation. DDP4 is a multifunctional protein that exhibits catalytic activity, acts as a binding protein, and serves as a ligand for various extracellular molecules. It is expressed on the surface of many cell types throughout the body, including those involved in immune function and inflammation.
DDP4 has been linked to immune regulation and cell growth, and it can interact with other molecules on the cell surface. For instance, it acts as a co-stimulatory molecule within the immune system, amplifying signals for T-cell activation. This immune function appears to be independent of its enzymatic activity. Its presence on various cell types and interactions suggest broader involvement in physiological processes, though these roles are still being investigated.