What are gastrointestinal hormones and which ones must you know?
Gastrointestinal (GI) hormones are peptides released into the portal blood by enteroendocrine cells scattered through the mucosa of the stomach and small intestine. They act on distant targets — the stomach, pancreas, gallbladder and gut smooth muscle — to regulate secretion, motility and growth. Most NEET PG and INI-CET questions on this topic are really four questions repeated in different clothes: which cell makes it, what releases it, what does it do, and what disease or test is linked to it.
| Hormone | Source cell and site | Main stimulus | Main actions |
|---|---|---|---|
| Gastrin | G cells — gastric antrum (also duodenum) | Peptides and amino acids, gastric distension, vagus via GRP, high gastric pH | Gastric acid secretion (via ECL cell histamine); trophic to gastric mucosa |
| Cholecystokinin (CCK) | I cells — duodenum and jejunum | Fatty acids and proteins in the duodenum | Gallbladder contraction, sphincter of Oddi relaxation, pancreatic enzyme secretion, slows gastric emptying, satiety |
| Secretin | S cells — duodenum | H⁺ (acid) and fatty acids in the duodenum | Pancreatic and biliary bicarbonate-rich fluid; reduces gastric acid |
| GIP | K cells — duodenum and proximal jejunum | Glucose, fat (stronger) and protein | Incretin: enhances glucose-dependent insulin release |
| Motilin | Mo cells — upper small intestine | Fasting state (cyclic release) | Triggers the migrating motor complex (hunger contractions) |
| Somatostatin | D cells — stomach, intestine, pancreatic islet δ cells | Low gastric pH, other hormones | Inhibits gastrin, CCK, secretin, VIP, insulin, glucagon and GH |
What does gastrin do and what controls its release?
Gastrin is made by G cells, found mainly in the pyloric antrum and also in the duodenum. It is released in response to vagal stimulation and gastrin-releasing peptide (GRP), to peptides and amino acids from a meal, to gastric distension and to a rise in gastric pH. Release is reduced by somatostatin from neighbouring D cells and by a fall in gastric pH — a classic negative-feedback loop that switches gastrin off once the stomach is acidic.
Gastrin travels in the blood to the gastric fundus and body, where it binds the CCK-B (CCK-2) receptor. It acts on two cells: the parietal cell, increasing H⁺/K⁺ ATPase expression and acid output, and the enterochromaffin-like (ECL) cell, which releases histamine that acts on H2 receptors of the parietal cell. Gastrin is also trophic: it stimulates growth of the gastric mucosa and promotes proliferation of parietal and ECL cells.
- Big gastrin (G-34, 34 amino acids) is the commonest circulating form; the bioactivity sits in the C-terminal pentapeptide, whatever the chain length.
- Pentagastrin has been used as a diagnostic aid — for example the pentagastrin-stimulated calcitonin test for medullary thyroid carcinoma.
- Gastrin assay is mainly requested to diagnose a gastrinoma (Zollinger-Ellison syndrome).
Which diseases raise gastrin, and how is Zollinger-Ellison syndrome diagnosed?
Because gastrin is switched off by acid, any state of low acid raises gastrin, while a gastrin-secreting tumour raises gastrin despite very high acid. Distinguishing the two is a favourite exam theme.
| Cause | Gastric acid | Mechanism |
|---|---|---|
| Zollinger-Ellison syndrome (gastrinoma) | Very high | Unregulated gastrin from a neuroendocrine tumour; parietal and ECL hyperplasia; refractory peptic ulcers and secretory diarrhoea |
| Pernicious anaemia / atrophic gastritis | Low (achlorhydria) | Loss of parietal cells removes acid feedback, so G cells over-secrete; trophic effect can cause ECL hyperplasia and carcinoid tumours |
| Proton pump inhibitors | Low | H⁺/K⁺ ATPase blockade reduces acid and gastrin rises; stopping a long course can cause a rebound refractory gastritis |
| H. pylori gastritis | Variable | Reduced somatostatin-secreting D cells disturbs control of G cells |
Zollinger-Ellison syndrome (ZES) is defined by the triad of gastrinoma, gastric acid hypersecretion and recurrent peptic ulcers, often with secretory diarrhoea. StatPearls describes the diagnosis as an elevated fasting serum gastrin far above 100 pg/mL together with increased basal acid output and/or a gastric pH below 2.0. The supporting test is the secretin stimulation test (see below). Tumour biopsy stains positive for chromogranin A, synaptophysin and gastrin.
What are the actions and receptors of cholecystokinin (CCK)?
Cholecystokinin is made by I cells of the duodenal and jejunal mucosa. Its main stimuli are fatty acids (long-chain, sensed through GPR40) and proteins/amino acids in the duodenal lumen. It acts on two G-protein-coupled receptors: CCK-1 (formerly CCK-A), found mainly in the periphery — gallbladder smooth muscle, pancreatic acinar cells and vagal afferents — and CCK-2 (formerly CCK-B), found mainly in the brain and stomach.
- Gallbladder contracts and the sphincter of Oddi relaxes, releasing bile for fat digestion.
- Pancreatic acinar cells release digestive enzymes (zymogen granules).
- Gastric emptying is slowed (relaxation of the proximal stomach and increased pyloric tension), so chyme enters the duodenum no faster than it can be digested.
- Gastric acid is reduced after a meal through effects on gastrin via somatostatin.
- Satiety — CCK acts through vagal afferents and the nucleus tractus solitarius to reduce food intake.
What does secretin do, and what is the secretin stimulation test?
Secretin was discovered by Bayliss and Starling in 1902, whose work showed that acid in the duodenum releases a blood-borne signal that makes the pancreas secrete — a finding that conflicted with the purely neural view held by the Pavlov school. It is a 27-amino-acid peptide produced by S cells in the duodenal mucosa and belongs to the same structural family as GIP, VIP and glucagon.
- Stimulus: acid (H⁺) and fatty acids in the duodenum.
- Main action: pancreatic ductal cells secrete bicarbonate-rich fluid through a cAMP mechanism, neutralising gastric acid so that pancreatic enzymes work at pH 6–8.
- Biliary bicarbonate secretion rises as well, and Brunner gland bicarbonate increases.
- Gastric acid secretion falls — secretin is an enterogastrone — and gastric motility is reduced.
Secretin stimulation test for gastrinoma. Normally secretin inhibits gastrin release. In a gastrinoma it paradoxically increases gastrin, and this response supports the diagnosis of ZES. Secretin is also used to assess pancreatic exocrine function and, in secretin-enhanced ERCP/MRCP, to show ductal anatomy and obstruction. In cystic fibrosis, the CFTR defect blunts the pancreatic chloride and bicarbonate response to secretin, producing thick, dehydrated secretions.
What do GIP, motilin and somatostatin do?
GIP (glucose-dependent insulinotropic polypeptide) is a 42-amino-acid hormone secreted by K cells concentrated in the duodenum and proximal jejunum. Both fat and carbohydrate stimulate it, with fat a stronger stimulus. It was the first incretin described: an oral glucose load triggers more insulin than the same glucose given intravenously. Its partner incretin GLP-1 comes from L cells of the distal gut (ileum and colon). After release, the enzyme DPP-4 removes the two N-terminal amino acids and inactivates GIP, which is why DPP-4 inhibitors raise incretin levels.
Motilin is a 22-amino-acid peptide from Mo cells of the duodenal mucosa. It is released cyclically in the fasting state and starts the migrating motor complex (MMC) — the 'housekeeper' wave that sweeps undigested food from the stomach to the terminal ileum about every 1.5 to 2 hours. The MMC has three phases: I quiescent, II increasing activity, III intense contractions (hunger contractions). Motilin levels fall after glucose or fat ingestion, and secretin and glucagon reduce motility while CCK, gastrin and motilin increase it.
Somatostatin exists as SS-14 (mainly in the brain) and SS-28 (mainly in the gut) and has a plasma half-life of only 1–3 minutes. About 65% of the body's somatostatin is in gut D cells. It is the great inhibitor: it suppresses gastrin, CCK, secretin, VIP, insulin, glucagon, growth hormone, TSH and prolactin and reduces gastric acid, pancreatic enzyme secretion and bile flow. Because of the short half-life, longer-acting analogues are used mainly in neuroendocrine tumours; excess production occurs in the rare somatostatinoma.
How are GI hormones asked in NEET PG and INI-CET?
- 'Which hormone is released from S cells / I cells / K cells / G cells?' — one-word source questions; learn the table in the first section.
- 'Which stimulates gallbladder contraction?' → CCK. 'Which stimulates bicarbonate secretion from the pancreas?' → secretin.
- 'Which acts on the CCK-B receptor?' → gastrin.
- ZES vignettes — recurrent ulcers, diarrhoea, fasting gastrin above 100 pg/mL, pH below 2; confirm with secretin test (paradoxical rise).
- Hunger contractions / MMC → motilin.
- Incretin effect → GIP and GLP-1; DPP-4 degrades them.
- Highest somatostatin content → gut D cells; long-acting somatostatin analogues treat neuroendocrine tumours.