Gastrointestinal hormones are released into the portal circulation (portal blood).
They act on target cells that have specific receptors for each hormone.
Their effects continue even if all nerve connections between the site of release and the site of action are cut.
Table 63.1 summarizes:
- The major gastrointestinal hormones.
- Their actions.
- The stimuli for their secretion.
- The sites where they are secreted.
Several gastrointestinal hormones also control gastrointestinal secretion.
Most of these hormones also affect gastrointestinal motility.
Their effects on motility are usually less important than their effects on secretion.
The important motility effects are described below.

Gastrin

Gastrin is secreted by G cells in the antrum of the stomach.
It is released in response to:
- Stomach distention
- Protein digestion products
- Gastrin-releasing peptide (GRP) released from gastric mucosal nerves during vagal stimulation
The main actions of gastrin are:
- Stimulates gastric acid secretion
- Stimulates growth of the gastric mucosa

Cholecystokinin (CCK)

CCK is secreted by I cells in the mucosa of the duodenum and jejunum.
It is released mainly in response to:
- Fat digestion products
- Fatty acids
- Monoglycerides in the intestinal contents
CCK strongly contracts the gallbladder.
This releases bile into the small intestine.
Bile helps emulsify fats and allows their digestion and absorption.
CCK also moderately inhibits stomach contractions.
Therefore, stomach emptying slows, giving more time for fat digestion in the upper small intestine.
CCK also promotes satiety (feeling of fullness).
It does this by stimulating sensory afferent nerve fibers in the duodenum.
These signals travel through the vagus nerve to the feeding centers of the brain, helping prevent overeating.

Secretin was the first gastrointestinal hormone discovered.
It is secreted by S cells in the mucosa of the duodenum.
It is released when acidic gastric juice enters the duodenum from the pylorus of the stomach.
Secretin has a mild effect on gastrointestinal motility.
It mainly stimulates pancreatic bicarbonate secretion.
Bicarbonate neutralizes the acid in the small intestine.

Glucose-dependent insulinotropic peptide (GIP) is also called gastric inhibitory peptide.
It is secreted by the mucosa of the upper small intestine.
It is released mainly in response to:
- Fatty acids
- Amino acids
It is released to a lesser extent by carbohydrates.
GIP slightly decreases stomach motor activity.
As a result, stomach emptying slows when the upper small intestine already contains a large amount of food.
At very low blood levels, even before affecting stomach motility, GIP stimulates insulin secretion.

Motilin is secreted by the stomach and upper duodenum.
It is released during fasting.
Its main function is to increase gastrointestinal motility.
Motilin is released cyclically.
It stimulates interdigestive myoelectric complexes.
These are waves of gastrointestinal contractions.
They pass through the stomach and small intestine about every 90 minutes in a fasting person.

Gastrointestinal hormones travel through the blood and act on specific receptors.
Their effects continue even without nerve connections.
Gastrin → Increases gastric acid secretion and gastric mucosal growth.
CCK → Contracts the gallbladder, slows stomach emptying, and promotes satiety.
Secretin → Stimulates pancreatic bicarbonate secretion to neutralize acid.
GIP → Slows stomach emptying and stimulates insulin secretion.
Motilin → Increases gastrointestinal motility during fasting by producing interdigestive myoelectric complexes every 90 minutes.

Protein enters the stomach → Gastrin is released → More gastric acid is produced.
Fat enters the duodenum → CCK is released → Gallbladder contracts and stomach emptying slows.
Acid enters the duodenum → Secretin is released → Pancreas secretes bicarbonate to neutralize the acid.
Food overloads the upper small intestine → GIP is released → Stomach empties more slowly and insulin secretion increases.
During fasting → Motilin is released every 90 minutes → Interdigestive myoelectric complexes sweep through the stomach and small intestine.

Figure Number: Table 63.1

Interdigestive myoelectric complexes occur approximately every 90 minutes during fasting.

Motilin secretion is inhibited after food is eaten.
Glucagon-like peptide-1 (GLP-1) is secreted by intestinal L-cells.
The number of L-cells is low in the duodenum and jejunum.
The number of L-cells gradually increases toward the lower parts of the intestine.
The highest number of L-cells is found in the ileum and colon.
The L-cells face the intestinal lumen.
Therefore, they directly detect nutrients present inside the intestine.
In healthy people, eating carbohydrates or proteins causes a rapid increase in blood GLP-1 levels within 10–15 minutes.
GLP-1 reaches its highest level about 30–60 minutes after eating carbohydrates or proteins.
Eating fats (lipids) causes a later but longer-lasting increase in GLP-1.
The important effects of GLP-1 include:
- Stimulates insulin secretion in a glucose-dependent manner.
- Inhibits stomach emptying.
- Inhibits gastric acid secretion.
- Promotes satiety (feeling of fullness).
- Reduces food intake.
Besides these gastrointestinal hormones, there are many other peptides and paracrine factors.
These substances also affect different gastrointestinal functions, including gastrointestinal motility.
Many of these are discussed in later chapters.

Motilin decreases after eating food.
GLP-1 is released from intestinal L-cells.
L-cells are most numerous in the ileum and colon.
Carbohydrates and proteins increase GLP-1 quickly (10–15 minutes), with a peak at 30–60 minutes.
Fats produce a later but longer-lasting increase in GLP-1.
GLP-1:
- Increases insulin secretion
- Slows stomach emptying
- Decreases gastric acid secretion
- Increases satiety
- Reduces food intake

After eating carbohydrates → GLP-1 rises within 10–15 minutes → Insulin secretion increases.
After eating a fatty meal → GLP-1 rises more slowly but lasts longer → Stomach empties more slowly and fullness lasts longer.
After a meal → Motilin secretion decreases → Interdigestive fasting contractions stop.

KEEP IN MIND : GLP-1 rises within 10–15 minutes, peaks at 30–60 minutes after carbohydrates/proteins; motilin is inhibited after food intake.)

MADE BY EASIEST AND SELF LEARNING BY CEO AND FOUNDER DR SHEEN