GLP-1 and GIP are released by the gut and amplify insulin secretion
Expansion
An oral glucose load produces two to three times more insulin than the same rise in blood glucose achieved intravenously. The difference is the incretin effect, accounting for 50 to 70 per cent of the insulin response to a meal.
Two hormones:
- GLP-1, from L cells of the ileum and colon
- GIP, from K cells of the duodenum and jejunum
GLP-1 actions
- Glucose-dependent stimulation of insulin secretion
- Suppression of glucagon
- Slowed gastric emptying
- Increased satiety
Both are rapidly degraded by dipeptidyl peptidase-4 (DPP-4), with a half-life of only 1 to 2 minutes.
The incretin effect is reduced in type 2 diabetes, which is the rationale for two drug classes: GLP-1 receptor agonists (resistant to DPP-4, and producing weight loss and cardiovascular benefit) and DPP-4 inhibitors (prolonging endogenous hormone, weight neutral).
Because the insulin effect is glucose-dependent, hypoglycaemia is uncommon unless combined with sulfonylureas or insulin.