Development of Dipeptidyl Peptidase-4 Inhibitors - DPP-4 Mechanism

DPP-4 Mechanism

During a meal the incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent gastric inhibitory polypeptide (GIP) are released from the small intestine into the vasculature. The hormones regulate insulin secretion in a glucose-dependent manner. GLP-1 has many roles in the human body; it stimulates insulin biosynthesis, inhibits glucagon secretion, slows gastric emptying, reduces appetite and stimulates regeneration of islet β-cells. GIP and GLP-1 have extremely short plasma half-lives due to a very rapid inactivation. The enzyme responsible for the metabolism is DPP-4. Inhibition of DPP-4 leads to potentiation of endogenous GIP and GLP-1 and hence improves treatment of type 2 diabetes (Figure 1).

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