GI hormones: gastrin, CCK, secretin, GIP and motilin
Each gut hormone answers one question: what has just arrived, and what must the gut do about it? Match every hormone to its source cell, its stimulus and its actions.
Chapters (11)
Match each major GI hormone (gastrin, cholecystokinin, secretin, GIP, motilin) to its source cell, stimulus and actions.
The short version
- Gastrin from G cells for acid, CCK from I cells for bile and enzymes, secretin from S cells for bicarbonate.
- GIP from K cells is the glucose-dependent insulin booster; motilin from M cells sweeps the gut between meals.
- The stimulus gives away the job: protein, acid, fat, glucose or an empty gut.
- The cell letters give the lineup: G, I, S, K, M.
- The old name "gastric inhibitory peptide" misleads: it blocked acid only at very high doses, and does not at normal levels in people.
Same blood glucose, different route: how the gut talks to the pancreas
Two volunteers follow exactly the same blood glucose curve. One drinks glucose; the other receives it through a vein, with the drip adjusted to match. The drinker releases far more insulin.[5]
The only difference is the route, so how does the gut talk to the pancreas? The answer is GI hormones, and this lesson matches each major one to its source cell, its stimulus and its actions.
GI hormones come from enteroendocrine cells scattered through the lining of the stomach and small intestine. The cells sample the contents of the lumen, then release hormone into the blood to reach distant targets.[1]
So the stimulus tells you the job: ask what has just arrived, and what the gut must do about it. The cell letters give the lineup.[1]
| Hormone | Cell | Where | Stimulus | Main actions |
|---|---|---|---|---|
| Gastrin | G | Gastric antrum | Peptides and amino acids; stomach stretch via the vagus | Acid secretion; growth of the acid-making lining |
| Cholecystokinin (CCK) | I | Duodenum and jejunum | Digested fat and protein | Gallbladder contraction; sphincter of Oddi relaxation; pancreatic enzymes; slower gastric emptying |
| Secretin | S | Duodenum | Acid arriving from the stomach | Bicarbonate-rich pancreatic fluid |
| GIP | K | Upper small intestine | Glucose, fat and some amino acids | Amplifies insulin release while glucose is high |
| Motilin | M | Duodenum and jejunum | Surges in cycles between meals | Starts migrating motility complexes |
Gastrin: G cells, the antrum and acid
G cells in the stomach antrum make gastrin. Peptides and amino acids release it, so does stretch through the vagus, and a very acidic stomach switches it off.[1]
Gastrin drives the parietal cells to make acid, mostly by first prompting histamine release from neighbouring ECL cells, and it feeds growth of the acid-making lining.[2][9]
Cholecystokinin (CCK): I cells, fat, protein and bile
I cells in the duodenum and jejunum make cholecystokinin, CCK. Digested fat and protein are its triggers.[3]
CCK contracts the gallbladder, relaxes the sphincter of Oddi and drives pancreatic enzyme secretion; it also slows gastric emptying.[3]
Blood levels stay tiny: from about 1 pmol/L when fasting to only 3–5 pmol/L after a meal.[3]
Secretin: S cells, acid and bicarbonate
S cells in the duodenum make secretin, and their trigger is acid arriving from the stomach.[4]
Secretin makes pancreatic duct cells pour out bicarbonate-rich fluid that neutralises that acid, and CCK amplifies the effect.[3][4]
GIP and the incretin effect: K cells and glucose-dependent insulin
K cells in the upper small intestine make GIP, now called glucose-dependent insulinotropic peptide. Glucose, fat and some amino acids release it.[5]
GIP amplifies insulin release, but only while glucose is high. That answers the opening puzzle: the drinker's gut senses glucose and releases incretin hormones, and the vein bypasses the gut completely.[5]
Motilin: M cells, migrating motility complexes and erythromycin
M cells make motilin, and it surges in cycles between meals; eating interrupts the cycle.[8]
It starts the migrating motility complexes, the housekeeping waves that sweep the empty gut.[1][8]
Erythromycin acts on the motilin receptor, which is why it speeds gastric emptying.[7]
Following a cheese sandwich through the gut
Protein and fat leave the stomach, and CCK arrives with bile and enzymes. The acidic chyme meets the duodenum, and secretin sends bicarbonate to meet it.
- Protein and fat reach the duodenumCCK is released: bile and pancreatic enzymes.
- Acidic chyme meets the duodenumSecretin is released: bicarbonate to neutralise the acid.
Each hormone answers its own question: protein, acid, fat, glucose or an empty gut.
Practice question
Original · USMLE styleA 30-year-old healthy volunteer takes part in a physiology study. A catheter infuses hydrochloric acid into the duodenum, and the luminal pH falls to 2.0. Pancreatic juice collected afterwards shows a marked rise in volume and bicarbonate concentration, with little change in enzyme output.
Common questions
What are the main GI hormones and where do they come from?
Gastrin comes from G cells, cholecystokinin (CCK) from I cells, secretin from S cells, GIP from K cells and motilin from M cells. All are made by enteroendocrine cells in the lining of the stomach and small intestine.
What does secretin do?
Secretin is released from S cells when acid arrives from the stomach. It makes pancreatic duct cells pour out bicarbonate-rich fluid that neutralises the acid.
What is the incretin effect?
A person who drinks glucose releases far more insulin than a person given glucose through a vein along the same blood glucose curve. The gut senses glucose and releases incretin hormones, GIP and GLP-1; GIP amplifies insulin release only while glucose is high.
Why is GIP called glucose-dependent insulinotropic peptide?
Its old name, gastric inhibitory peptide, misleads: it blocked acid only at very high doses, and does not at normal levels in people. Its real job is amplifying insulin release while glucose is high.
Why does erythromycin speed gastric emptying?
Erythromycin acts on the motilin receptor, and motilin starts the migrating motility complexes that sweep the empty gut.
Transcript
Read the full narration, by chapter675 words
0:00Same glucose, different route: the puzzle
Two volunteers follow exactly the same blood glucose curve. One drinks glucose, and the other gets it through a vein, with the drip adjusted to match. The drinker releases far more insulin. The only difference is the route, so how does the gut talk to the pancreas? Today: match each major gut hormone to its source cell, its stimulus and its actions.
0:24Enteroendocrine cells and the colour key
These hormones come from enteroendocrine cells scattered through the lining of the stomach and small intestine. The cells sample the contents of the lumen, then release hormone into the blood to reach distant targets. So the stimulus tells you the job: ask what has just arrived, and what the gut must do about it.
0:44G cells: gastrin, acid and the parietal cell
The cell letters give the lineup: G, I, S, K, M. G cells, in the stomach antrum, make gastrin. Peptides and amino acids release it, so does stretch through the vagus, and a very acidic stomach switches it off. Gastrin drives the parietal cells to make acid, mostly by first prompting histamine release from neighbouring ECL cells, and it feeds growth of the acid-making lining.
1:11I cells: cholecystokinin (CCK)
I cells, in the duodenum and jejunum, make cholecystokinin, CCK. Digested fat and protein are its triggers. CCK contracts the gallbladder, relaxes the sphincter of Oddi, and drives pancreatic enzyme secretion; it also slows gastric emptying. Blood levels stay tiny: from about one picomole per litre when fasting to only three to five after a meal.
1:39S cells: secretin and bicarbonate
S cells, in the duodenum, make secretin, and their trigger is acid arriving from the stomach. Secretin makes pancreatic duct cells pour out bicarbonate-rich fluid that neutralises that acid, and CCK amplifies the effect.
1:55K cells: GIP and the incretin effect
K cells, in the upper small intestine, make GIP, now called glucose-dependent insulinotropic peptide. Glucose, fat and some amino acids release it. GIP amplifies insulin release, but only while glucose is high. That answers our opening puzzle: the drinker's gut senses glucose and releases incretin hormones, and the vein bypasses the gut completely. GLP-1, from L cells, is the other major incretin. The old name, gastric inhibitory peptide, misleads: it blocked acid only at very high doses, and does not at normal levels in people.
2:37M cells: motilin and erythromycin
M cells make motilin, and it surges in cycles between meals; eating interrupts the cycle. It starts the migrating motility complexes, the housekeeping waves that sweep the empty gut. Erythromycin acts on the motilin receptor, which is why it speeds gastric emptying. Now follow a cheese sandwich.
2:56Follow a cheese sandwich
Protein and fat leave the stomach, and CCK arrives with bile and enzymes. The acidic chyme meets the duodenum, and secretin sends bicarbonate to meet it. Each hormone answers its own question: acid, fat, glucose, or an empty gut.
3:15Practice question
Your turn. A 30-year-old healthy volunteer takes part in a physiology study. A catheter infuses hydrochloric acid into the duodenum, and the luminal pH falls to 2.0. Pancreatic juice collected afterwards shows a marked rise in volume and bicarbonate concentration, with little change in enzyme output. Release of which of the following is the most likely cause? A, cholecystokinin, from I cells. B, gastrin, from G cells. C, GIP, from K cells. D, motilin, from M cells. E, secretin, from S cells. Pause here and decide.
4:02The wrong options, then the answer
A is out: CCK responds mainly to fat and protein, and its main pancreatic effect is enzyme secretion, which barely changed. B is out: gastrin acts on the stomach, and it is released by peptides and stretch, not by duodenal acid. C is out: GIP responds to glucose, fat and amino acids, and boosts insulin. D is out: motilin works between meals and moves the gut, rather than secreting bicarbonate. So the answer is E. Acid in the duodenum releases secretin, and secretin drives bicarbonate-rich pancreatic juice.
4:43Recap pocket card and next lesson
Three things to keep. One: gastrin from G cells for acid, CCK from I cells for bile and enzymes, secretin from S cells for bicarbonate. Two: GIP from K cells is the glucose-dependent insulin booster, and motilin from M cells sweeps the gut between meals. Three: the stimulus gives away the job. Next, gastric acid secretion and the parietal cell.
Sources
Numbers in the text, e.g. [1], point here- OpenStax Anatomy & Physiology 2e, 23.2 Digestive System Processes and Regulation; 23.4 The Stomach; 23.5 The Small and Large Intestines: openstax.org/books/anatomy-and-physiology-2e
- MSD Manual Professional Version, Overview of Acid Secretion (Jan 2025): msdmanuals.com/professional
- Rehfeld JF. Cholecystokinin: From Local Gut Hormone to Ubiquitous Messenger. Front Endocrinol 2017: europepmc.org/article/PMC/PMC5389988
- Pancreatic endocrine and exocrine signaling and crosstalk (2025): europepmc.org/article/PMC/PMC11825823
- GIP review (2025), incretin effect and the naming of GIP: europepmc.org/article/PMC/PMC11931254
- Incretin therapies review (2016): europepmc.org/article/PMC/PMC4785614
- Evolving prokinetic therapy, 2026 (erythromycin and motilin receptor): europepmc.org/article/PMC/PMC13248104
- Motilin LC-MS study, 2024 (fasting cycle, meal interrupts): europepmc.org/article/PMC/PMC10965782
- Gastrin and H. pylori carcinogenesis, 2026 (ECL cell, trophic effect): europepmc.org/article/PMC/PMC13457304
- GIP/GIPR editorial, 2025 (original name): europepmc.org/article/PMC/PMC12560088
The CCK blood levels, the glucose curves, the insulin bars and the GIP graph are schematic teaching drawings; the graphs carry no values.
The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.
Image credits. Illustrations: Servier Medical Art (smart.servier.com), CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/), adapted (cropped, upscaled, recoloured, outlined): stomach, duodenum, pancreas, liver with gallbladder, fundic gland mucosa, parietal cell, water glass, bread, fatty food, islet of Langerhans, syringe. Capsule icon: "pill_blue" by Marcel Tisch via bioicons.com, CC0. The enteroendocrine cell sketches, hormone arrows, number line, schematic graphs, question card, pocket card and all handwriting are drawn in code (original). No AI-generated anatomy, labels or graphs.
Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-GI-001.
For exam study only, not medical advice. Read the medical disclaimer.