Gastrointestinal Hormones
On this page
Direct answer
The gastrointestinal tract is the body's largest endocrine organ, its enteroendocrine cells releasing peptides that coordinate digestion with the meal: gastrin from antral G cells drives gastric acid and mucosal growth; secretin from duodenal S cells releases alkaline pancreatic juice and bile in response to acid; cholecystokinin from I cells contracts the gallbladder, relaxes the sphincter of Oddi and stimulates enzyme-rich pancreatic secretion; GIP and GLP-1 (the incretins) amplify insulin release for the absorbed meal; and motilin initiates the migrating motor complex in the fasting state. Most act additionally in paracrine (histamine, somatostatin) or neurocrine (VIP, gastrin-releasing peptide) modes.
What you must remember
- Gastrin: G cells, antrum (and duodenum); stimulated by peptides, gastric distension and gastrin-releasing peptide (vagal), inhibited by luminal pH below 3 via somatostatin from D cells; actions — gastric acid (via ECL-cell histamine), trophic on oxyntic mucosa; hypergastrinaemia in Zollinger-Ellison syndrome and pernicious anaemia (achlorhydria removes the brake).
- Secretin: S cells, duodenal mucosa; released by luminal pH below 4.5; stimulates pancreatic and biliary bicarbonate, inhibits gastric acid and motility — "nature's antacid"; used clinically as the secretin stimulation test for gastrinoma (paradoxical rise) and in secretin-enhanced MRCP.
- Cholecystokinin: I cells, duodenum and jejunum; released by fatty acids and amino acids; contracts gallbladder, relaxes sphincter of Oddi, stimulates pancreatic enzymes, slows gastric emptying (the fat-mediated enterogastric brake) and promotes satiety.
- Incretins: GIP from K cells (duodenum, glucose and fat) and GLP-1 from L cells (ileum-colon, nutrients); both glucose-dependent insulin amplification, GLP-1 additionally suppresses glucagon, slows gastric emptying and signals satiety — degraded within minutes by DPP-4, the target of gliptins and the backbone of GLP-1 receptor agonists such as semaglutide.
- Motilin: Mo cells, cyclical release every 90-120 minutes in fasting; triggers migrating motor complex phase III ("housekeeper" waves); erythromycin is an agonist explaining its prokinetic use and diarrhea as a side effect.
- Paracrine and neurocrine regulators: histamine (ECL cells, the final common amplifier of acid), somatostatin (D cells, universal inhibitor), VIP (neurocrine relaxation and secretion — Verner-Morrison watery diarrhoea syndrome).
- Cell-type shorthand for vivas: G-gastrin, S-secretin, I-CCK, K-GIP, L-GLP-1, Mo-motilin, D-somatostatin, ECL-histamine.
How to work through a meal, hormone by hormone
Food enters the stomach: distension and peptides trigger vagal GRP and direct stimulation of G cells; gastrin rises, ECL cells release histamine, and histamine plus gastrin plus vagal acetylcholine converge on the parietal cell — the three-ligand model that explains why H2 blockers partially and proton pump inhibitors completely shut acid off. Acidified chyme (pH below 4.5) then hits the duodenum: secretin pours out bicarbonate from pancreas and liver to neutralise it, while CCK, riding on the fat and protein content, delivers enzymes and bile at the exact moment nutrients need emulsification.
In the fasting state a different clock runs: every 90-120 minutes motilin spikes and sweeps residual debris and bacteria caudad — the migrating motor complex that ceases the moment you feed the patient, a reason continuous feeding predisposes to bacterial overgrowth. Now apply it to disease: a patient with recurrent duodenal ulcers, diarrhoea and high gastrin has Zollinger-Ellison (gastrinoma, often duodenal or pancreatic); secretin injection paradoxically raises gastrin (the tumour's receptors respond in the wrong direction), while physiological gastrin would simply be suppressed. The diabetic on a GLP-1 agonist who reports early satiety and nausea is experiencing the hormone's physiologic actions — delayed gastric emptying and central satiety — as pharmacology.
Where students slip
The exam trap is calling all GI peptides hormones in the strict sense; histamine and somatostatin are paracrine, VIP and GRP are neurocrine, and only the classical five travel bloodstream distances — the modes of transmission are themselves a standard short-question. The second trap is the secretin paradox: students expect suppression and cannot explain the gastrinoma's rise — secretin receptors on the tumour trigger release, a diagnostic exception worth quoting with its basis. Finally, candidates mix the I and S cells (CCK and secretin), and mix GIP with GLP-1 origins; the safest anchor is the meal sequence — acid first (secretin), then fat (CCK), then glucose across the mucosa (incretins from K then L cells in sequence along the bowel).
Frequently asked questions
Which GI hormone is released by acid and what does it do?
Secretin, from duodenal S cells when luminal pH falls below 4.5; it stimulates pancreatic ductal and biliary bicarbonate secretion while inhibiting gastric acid and motility.
Why is CCK called the gallbladder and pancreas hormone?
Because fatty acids and amino acids in the duodenum release it from I cells to contract the gallbladder, relax the sphincter of Oddi and secrete pancreatic enzymes — coordinating bile and enzyme delivery to the meal.
What is the incretin effect?
Oral glucose evokes more insulin than intravenous glucose because GIP and GLP-1 released from the gut amplify beta-cell secretion; DPP-4 inhibitors prolong GLP-1 while receptor agonists mimic it.
What stimulates motilin and what does it do?
Cyclical fasting-state release every 90-120 minutes from Mo cells; it initiates phase III of the migrating motor complex, the housekeeping contractions cleared by erythromycin-type agonists.
How does somatostatin regulate gastrin?
D-cell somatostatin tonically inhibits G cells, and luminal acidification enhances this; with achlorhydria (pernicious anaemia) or proton pump inhibitor therapy, the brake is released and gastrin rises hyperplastically.