In a patient with type 2 diabetes mellitus, the incretin effect is markedly reduced. Which of the following correctly explains the incretin effect and its impairment in T2DM?
- A Incretin effect refers to the ability of intestinal hormones to reduce glucagon; its loss in T2DM causes postprandial hyperglucagonemia as the only mechanism of hyperglycemia
- B Oral glucose elicits a 2–3 times greater insulin response than IV glucose producing identical plasma glucose levels; GLP-1 (from L-cells) and GIP (from K-cells) mediate this by stimulating pancreatic β-cells in a glucose-dependent manner; in T2DM, GLP-1 secretion is reduced and GIP responsiveness of β-cells is impaired ✓
- C The incretin effect is mediated solely by GLP-1; its loss increases gastric emptying rate, delivering a glucose bolus that overwhelms insulin secretion
- D Incretin effect refers to enhanced glucose uptake in muscle by GLP-1 acting on GLUT4 transporter insertion independent of insulin
Explanation
The incretin effect quantifies the enhanced insulin secretory response when glucose is given orally versus intravenously at matched plasma glucose levels — normally 50–70% of postprandial insulin secretion is attributable to incretins. GIP (glucose-dependent insulinotropic polypeptide, from K-cells of duodenum/jejunum) and GLP-1 (glucagon-like peptide-1, from L-cells of ileum/colon) act on their respective Gs-coupled receptors on β-cells, raising cAMP and potentiating glucose-stimulated insulin secretion in a strictly glucose-dependent manner (no effect at fasting glucose levels, preventing hypoglycemia). In T2DM, GLP-1 secretion is modestly reduced, but more importantly the insulinotropic response to GIP is severely blunted while the GLP-1 response is partially preserved (hence GLP-1 receptor agonists are effective therapeutically). Options B, C, and D represent incomplete or incorrect characterizations of the incretin mechanism.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.