Source of Gastric emptying

{{Infobox concept | name = Gastric emptying | subtitle = Gastrointestinal physiology | 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 }} '''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.{{r|marathe2013}} Delayed emptying is one of the principal actions of [[GLP-1 receptor agonist|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.{{r|marathe2013}} 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|exenatide]] and lixisenatide than for weekly agents.{{r|drucker2018}} == Normal physiology == 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.{{r|marathe2013}} 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, [[Glucagon-like peptide-1|GLP-1]], peptide YY and neural reflexes — the so-called ileal brake.{{r|holst2007}} 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 == GLP-1 receptor agonism delays emptying through vagal pathways and through direct action on gastric smooth muscle, increasing fundic compliance and pyloric tone.{{r|drucker2018}} 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.{{r|marathe2013}} Three clinical consequences follow. First, postprandial glucose control is contributed to differently by short- and long-acting agents.{{r|nauck2016}} Second, nausea correlates with the degree of delay, and the attenuation of the delay tracks the attenuation of nausea. Third, and more recently recognised, residual gastric contents after conventional fasting periods have prompted revised preoperative guidance; see [[Aspiration risk under anaesthesia]]. == Interaction with oral drugs == Delaying emptying alters the absorption profile of oral medicines. For most drugs the effect is on rate rather than on extent, so total exposure is unchanged and the practical consequence is small.{{r|marathe2013}} It matters where the timing of a peak concentration is what produces the effect — analgesics taken for acute pain, for instance — and where a drug has a narrow therapeutic index and is dosed against a target concentration. The oral contraceptive and levothyroxine are the interactions most often examined; reported effects have generally been modest. The reverse consideration also applies. [[Oral semaglutide|Oral semaglutide]] absorption depends on gastric conditions and on a strict fasting window, so anything that alters emptying alters its exposure — including, self-referentially, the delayed emptying produced by the drug itself.{{r|drucker2018}} == References == {{reflist}} <ref name="marathe2013">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.</ref> <ref name="drucker2018">Drucker DJ. "Mechanisms of action and therapeutic application of glucagon-like peptide-1." ''Cell Metabolism'' 27(4):740–756 (2018). PMID 29617641.</ref> <ref name="holst2007">Holst JJ. "The physiology of glucagon-like peptide 1." ''Physiological Reviews'' 87(4):1409–1439 (2007). PMID 17928588.</ref> <ref name="nauck2016">Nauck MA, Meier JJ. "The incretin effect in healthy individuals and those with type 2 diabetes." ''The Lancet Diabetes & Endocrinology'' 4(6):525–536 (2016). PMID 26876794.</ref> == See also == * [[Glucagon-like peptide-1]] * [[GLP-1 receptor agonist]] * [[Satiety signalling]] * [[Aspiration risk under anaesthesia]] * [[Exenatide]] {{DEFAULTSORT:Gastric emptying}} [[Category:Gastrointestinal physiology]] [[Category:Incretin biology]] [[Category:Adverse effects]]