Gastric emptying (revision 7)
Old revision·01:02, 6 Nov 2024·AnalyticalAnnie
| Gastric emptying | |
|---|---|
| Measured by | Scintigraphy, breath test, paracetamol absorption |
| Normal half-emptying time | ≈45–90 min for a solid meal |
| Effect of GLP-1 agonism | Delay, attenuating with continued exposure |
| Topic infobox · conventions | |
Gastric emptying is the rate at which the contents of the stomach are delivered to the duodenum. It is regulated by fundic tone, antral contraction and pyloric resistance, and is modulated by feedback from nutrients already in the small intestine — the mechanism by which Glucagon-like peptide-1 and other gut hormones slow it.[1]
Delayed emptying is one of the principal actions of GLP-1 receptor agonists. It blunts the postprandial glucose excursion by delivering carbohydrate to the absorptive surface more slowly, and it contributes to early satiety through gastric distension. In short-acting agonists it accounts for a substantial part of the postprandial glycaemic effect.[1]
The delay attenuates with continued exposure to a long-acting agonist — a rare instance of clinically relevant tachyphylaxis in this class — which is why the glycaemic contribution of delayed emptying is larger for short-acting agents such as exenatide and lixisenatide than for weekly agents.[2]
Normal physiology
[edit]Liquids empty approximately exponentially and rapidly; solids empty after a lag phase during which food is triturated to particles small enough to pass the pylorus, then at an approximately linear rate. A half-emptying time of about 45–90 minutes is usual for a standard solid meal, with wide interindividual variation.[1]
Rate is regulated to deliver nutrient to the small intestine at a roughly constant caloric rate, near 2 kcal per minute, regardless of meal composition. The regulator is feedback from nutrient sensing in the duodenum and ileum, mediated by cholecystokinin, GLP-1, peptide YY and neural reflexes — the so-called ileal brake.[3]
Measurement methods are not interchangeable. Scintigraphy is the reference technique; the ¹³C-octanoate breath test is a validated surrogate; paracetamol absorption is convenient but measures liquid-phase emptying only. A study reporting "delayed emptying" without naming its method is not comparable with one that names a different method.
Effect of incretin agonists
[edit]GLP-1 receptor agonism delays emptying through vagal pathways and through direct action on gastric smooth muscle, increasing fundic compliance and pyloric tone.[2]
The magnitude depends on the exposure profile. A short-acting agonist producing peaks and troughs delays emptying strongly at each peak; a continuously present long-acting agonist produces a delay that diminishes over weeks. The mechanism of that attenuation is thought to be receptor desensitisation on the relevant neurons, and it is one of the clearest examples of tachyphylaxis in incretin pharmacology.[1]
References
- ^ a b c d Marathe CS, Rayner CK, Jones KL, Horowitz M. "Relationships between gastric emptying, postprandial glycemia, and incretin hormones." Diabetes Care 36(5):1396–1405 (2013). DOI:10.2337/dc12-1609. PMID 23613599.
- ^ a b Drucker DJ. "Mechanisms of action and therapeutic application of glucagon-like peptide-1." Cell Metabolism 27(4):740–756 (2018). PMID 29617641.
- ^ Holst JJ. "The physiology of glucagon-like peptide 1." Physiological Reviews 87(4):1409–1439 (2007). PMID 17928588.