A patient with type 2 diabetes on metformin is started on a DPP-4 inhibitor (sitagliptin). The mechanism by which DPP-4 inhibitors increase insulin secretion is MOST accurately described as:
- A Direct stimulation of pancreatic beta-cell KATP channels causing membrane depolarisation and calcium influx
- B Stimulation of GLP-1 synthesis in intestinal L cells by a direct transcriptional mechanism
- C Prevention of degradation of GLP-1 and GIP secreted postprandially from gut L and K cells, increasing their half-lives and allowing glucose-dependent insulin secretion ✓
- D Inhibition of hepatic glucagon release via direct portal vein action
Explanation
DPP-4 (dipeptidyl peptidase-4) is a serine protease expressed on enterocytes, endothelium, and T-lymphocytes that rapidly inactivates GLP-1 (half-life ~2 minutes) and GIP after meal-induced secretion from intestinal L and K cells respectively. DPP-4 inhibitors extend the plasma half-life of endogenous intact (active) GLP-1 and GIP to ~10 minutes, allowing these incretins to act on pancreatic beta cells to stimulate glucose-dependent insulin secretion and on alpha cells to suppress glucagon — only in the hyperglycaemic state. They do not increase GLP-1 synthesis or directly act on KATP channels (which is sulphonylurea's mechanism).
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.