Gastrointestinal

Hormones

Assist. Prof. Dr. Gülbahar BÖYÜK ÖZCAN

Hormonal Control of Gastrointestinal Motility
Fundus Antrum Duo Jejun İleum Colon

Gastrin
CCK
Secretin
GIP
Motilin
CELLS SECRETING THE
HORMONES
• Enteroendocrine Cells
• Enteroendocrine cells are the hormone-
secreting cells in GI tract.
• These are the nerve cells and glandular
cells which are present in the gastric
mucosa, intestinal mucosa and the
pancreatic cells
• Neuroendocrine Cells or APUD Cells
• Enteroendocrine cells which secrete hormones from amines are
known as amine precursor uptake and decarboxylation cells (APUD
cells) or neuroendocrine cells.
• For the synthesis of a GI hormone, first a precursor substance of an
amine is taken up by these cells.
• Later, this precursor substance is decarboxylated to form the amine.
• From this amine, the hormone is synthesized.
• Because of the uptake of the amine precursor and decarboxylation of
this precursor substance, these cells are called APUD cells.
Enterochromaffin Cells
• Enteroendocrine cells which secrete serotonin are called
enterochromaffin cells.
• Histamine:
• • Produced by enterochromaffin-like cells (ECL cells) of the stomach.
• • Release is stimulated by gastrin.
• • Action: increase HCl secretion from parietal cells (major factor in
HCl secretion).
DESCRIPTION OF
GASTROINTESTINAL
HORMONES
Gastrin

• Produced from G cells in the antrum of the

stomach and to a lesser extent in the proximal
portion of the duodenum
• Release is increased by stomach distension,
peptides, amino acids, caffeine,
parasympathetic innervation
• Release is inhibited by highly acidic pH (< 2.0)
• Functions include:
• Increases gastric secretions (primarily
HCl)
• Increases histamine release;
• Increases gastric motility;
• stimulates growth of gastric mucosa
 Stimulation Of Gastric Acid Secretion

• Enterochromaffin-like (ECL) cells

• Neurotransmitter PACAP (pituitary adenyl cyclase activating peptide)
• GRP (gastrin releasing peptide)
Gastrin = hormone produced by stomach.

• Triggered by entry of
food into the
stomach, and the
Gastrin +
stretching of the
stomach
 Gastrin
• Enters the
bloodstream
→→→→

• goes back to
Gastrin +
the stomach
affecting the
 Gastrin

• Promotes the
release of HCl &,
stomach churning
Gastrin +
Secretin
• Secretin is produced in S cells in the duodenal and proximal jejunal mucosa
• Secretion is stimulated by arrival of acidic chyme in duodenum
• Functions include:
• Stimulates bicarbonate secretion from pancreas
• Inhibits gastric secretion by inhibiting gastrin release
• Decreases gastric motility
• Increases hepatic bile production, increases CCK
• Promotes growth and maintenance of the pancreas
Secretin = hormone produced in
cells of the small intestine

• Triggered by HCl acid in the

chyme
• enters bloodstream and
stimulates pancreatic cells.
• Response = Output of sodium
bicarbonate buffer.
Secretin = hormone produced in
cells of the small intestine

• ALSO, stimulates
the liver to produce
bile

First hormone discovered • BILE = emulsifies FAT

CCK = hormone produced in cells of the
small intestine

• Triggered by
CCK partially digested
protein & fat that
enters the sm.
intestine

CC
K
CCK = hormone produced in cells of the
small intestine

• Stimulates Gallbladder
contraction to release bile
• Stimulates Pancreas to
release enzymes
• Reduces appetite
 • Stimulation of insulin secretion

Gastric • Induces satiety

• In large doses, decreases gastric acid secretion

Inhibitory • In large doses, decreases the motor activity of

the stomach and therefore slows gastric
emptying when the upper small intestine is
already full of food products.
Peptide • Stimulates the activity of lipoprotein lipase in
adipocytes

(GIP) • Protects beta-cells of the pancreas from

destruction by apoptosis
Gastric Inhibitory
Peptide (GIP)
• GIP is synthesized and secreted by K cells, which
reside mainly in the proximal duodenum and to a
lesser extent in the jejunum
• Release is stimulated in response to Chyme rich in
triglycerides, fatty acids, and glucose in the small
intestine
• Functions:
• Stimulates release of insulin by beta cells
• Inhibits gastric secretion and motility
• Stimulates lipogenesis by adipose tissue
• Stimulates glucose use by skeletal muscle
cells
VASOACTIVE INTESTINAL POLYPEPTIDE
• Vasoactive intestinal polypeptide (VIP) contains 28 amino acid residues. This polypeptide is
secreted in the stomach and small intestine. A small amount of this hormone is also secreted in
large intestine.
• Stimulant for Secretion
• Presence of acid chyme in the stomach and intestine causes secretion of VIP.
• Actions
• Vasoactive intestinal polypeptide (VIP):
• i. Dilates splanchnic (peripheral) blood vessels.
• ii. Inhibits hydrochloric acid secretion in gastric juice.
• iii. Stimulates secretion of succus entericus with large amounts of electrolytes and water.
• iv. Relaxes smooth muscles of intestine.
• v. Augments action of acetylcholine on salivary glands.
• vi. Stimulates insulin secretion.
GLUCAGON
• Glucagon has 29 amino acid residues. It is secreted mainly by alpha cells of islets of
Langerhans in pancreas. It is also secreted by A cells in the stomach and L cells in the
intestine. In intestine, it is secreted as preproglucagon.
• Stimulant for Secretion
• Presence of food with more fat and protein in the stomach is the stimulant for
glucagon secretion in stomach and duodenum. Hypoglycemia is the stimulant for
secretion of pancreatic glucagon.
• Action
• Glucagon increases blood sugar level
 GLICENTIN
• Glicentin polypeptide is secreted by L cells in duodenum and jejunum and α-cells of pancreatic
islets. It is also secreted in brain.
• Precursor of this hormone is the preproglucagon. In intestine, the preproglucagon is converted into
glicentin and glucagon-like polypeptide-2 (GLP-2).
• In pancreas, it is converted into glucagon, glucagon-like polypeptide-1 (GLP-1) and major
proglucagon fragment.
• Stimulant for Secretion
• Glicentin is secreted when chyme with fat and protein enters the intestine.
• Action
• Like glucagon, glicentin also increases the blood sugar level.
Glucagon-like peptide-1
(GLP-1)
• Glucagon-like polypeptide-2 (GLP-2) is secreted by L cells in ileum and colon.
• Stimulant for Secretion
• Presence of food with glucose in the small intestine
• stimulates the release of GLP-1.
• Actions
• Decreases gastric emptying
• Induces satiety
• Increases sensitivity of pancreatic beta-cells to glucose.
Somatostatin
• Well known for its inhibitory physiological actions in multiple
targets, somatostatin can function via endocrine, paracrine,
or neurocrine pathways. Somatostatin is involved in a variety
of effects, and it is unclear whether its effects on the energy
balance are direct or indirect, as somatostatin inhibits the
release of numerous hormones
Somatostatin
• Produced by D cells of the stomach
• Secretion is stimulated by activation of the sympathetic nervous
system and by acidic pH,
• and is inhibited by activation of the parasympathetic nervous system,
continuously released, overridden by gastrin and nerves
• Functions include:
• Inhibit gastrin and histamine secretion
• also directly inhibits acid release from parietal cells
PANCREATIC POLYPEPTIDE
• Source of Secretion
• Pancreatic polypeptide is a polypeptide with 36 amino acid residues. It is
secreted mainly by the PP cells of the islets of Langerhans in pancreas. It
is also found in small intestine.
• Stimulant for Secretion
• Pancreatic polypeptide is secreted by the presence of chyme with
proteins in the small intestine. It is also secreted in conditions like
hypoglycemia, fasting and exercise.
• Actions
• Pancreatic polypeptide:
• i. Increases the secretion of glucagon from α-cells of islets of
Langerhans in pancreas.
• ii. Decreases the secretion of pancreatic juice from exocrine part of
pancreas.
 PEPTIDE YY
• Polypeptide YY with 36 amino acid residues, is structurally related to
pancreatic polypeptide and neuropeptide Y. It is secreted in L cells of ileum
and colon.
• Stimulant for Secretion
• Presence of fat-containing chyme stimulates the release of peptide YY
• Actions
• Peptide YY:
• i. Inhibits gastric secretion and motility
• ii. Reduces secretion of pancreatic juice
• iii. Inhibits the intestinal motility and stops passage of bowel beyond ileum
(ileal brake)
• iv. Suppresses appetite and food intake.
 NEUROPEPTIDE Y
• Neuropeptide Y contains 36 amino acid residues. It is structurally
related to pancreatic polypeptide and peptide YY. It is secreted by
enteric nerve endings particularly in ileum and colon. It is also
secreted in medulla, hypothalamus and neurons of autonomic
nervous system (ANS).
• Stimulant for Secretion
• Secretion of neuropeptide Y is stimulated by fat containing chyme.
• Action
• Neuropeptide Y increases the blood flow in enteric blood vessels
and stimulates food intake
 MOTILIN
• Motilin is built by 22 amino acid residues. It is secreted by Mo cells,
which are present in stomach and intestine.
• It is also believed to be secreted by enterochromoffin cells of intestine.
• Stimulant for Secretion
• Motilin is secreted when the chyme from stomach enters the duodenum.
• Actions
• Motilin:
• i. Accelerates gastric emptying
• ii. Increases the mixing and propulsive movements of small intestine
• iii. Increases the peristalsis in colon.
SUBSTANCE P
• Source of Secretion
• Substance P is a neurotransmitter with 11 amino acid
residues. It is secreted at the pain nerve endings in brain
and enteric nerve endings in small intestine
• Stimulant for Secretion
• Secretion of substance P in intestine is caused by the
presence of chyme.
• Actions
• In GI tract, substance P increases the mixing and
propulsive movements of small intestine
Hunger Hormones
• Hunger – a feeling of discomfort or weakness
caused by a lack of food

• Satiety – a feeling of fullness

 GHRELIN
• Ghrelin is a recently discovered hormone. This 28
amino acid polypeptide is synthesized by epithelial
cells in the fundus of stomach. It is also produced in
smaller amounts in hypothalamus, pituitary, kidney
and placenta.
• Stimulant for Secretion
• Secretion of ghrelin increases during fasting and
• decreases when stomach is full.
Hunger Hormones
Enterogastrone
• Source: It is secreted by the duodenal epithelium.
• Stimulus for secretion: Chyme entry into the duodenum
• Target organ: Stomach
• Action:
• It slows down gastric contractions to delay its emptying.
• It stops the secretion of gastric juice.
Enterogastrone
• Hormone produced
in small intestine
Entero- • Triggered by acid -
gastrone - rich chyme filled
with lipids.
• Target cells in the
stomach and blocks
gastrin
• Slows digestion b/c
digestion of fats
takes more time
Enterogastrone

• Inhibits peristalsis
Entero- and acid secretion
gastrone - of the stomach

• Slows digestion in
the stomach.
Villikinin

Stimulus for
Source: Intestinal Target organ: Small
secretion: Food in Action:
epithelium intestine
the small intestine
• It accelerates the
movement of villi to
increase the flow of
blood and lymph
and to enhance
absorption.
Duocrinin:
• Source: Intestinal epithelium
• Stimulus for secretion: Acidic chyme in the small intestine
• Target organ: Small intestine
• Action:
It stimulates Brunner’s glands for the secretin of viscous mucus so that
duodenum is protected from the acidic digestive enzymes secreted by the
stomach.
Enterocrinin:
Source: Intestinal epithelium
Stimulus for secretion: Acidic chyme in the small intestine
Target organ: Small intestine
Action:
It stimulates Crypts of Lieberkuhn to release a group of digestive enzymes
called carhohydrases (amylase, proteases, and lipases) that bring about the
complete digestion of food.
Oxyntomodulin
• Oxyntomodulin inhibits gastric secretion, pancreatic exocrine
secretion, and gastric emptying.
• Oxyntomodulin also inhibits food intake, in part, due to the
suppression of ghrelin levels
• Oxyntomodulin also exhibits incretin activity albeit modest
compared to that of GLP-1
 • The pancreas: - endocrine portion –
hormones
• - exocrine portion – the pancreatic juice
• The pancreatic juice: 1-2 1/24 hours,
colorless, viscous fluid
PANCREATIC
• (1-2 % of substances), alkaline (pH = 7.5 –
SECRETION 8.5),with a high HCO3 – content – from
gastric
• venous blood.
• The most important pancreatic digestive
enzymes:
Regulation of pancreatic secretion:

• – neural,
• – hormonal
• 1st – neural – 1-2 minutes – after the start of the feeding – via n.
vagus ⇒ the juice containing
• a high concentration of the enzymes - up 10%.
• Unconditioned and conditioned reflexes from the mouth ...
• Blockade with atropine.
Regulation of pancreatic secretion:
• 2nd – Neural + hormonal – gastric – distention – n. vagus
• - gastrin – large quantities of the enzymes
• 3rd – Hormonal – also in denervated pancreas - via GIT hormones:
• - Secretin – from „S cells“ – duodenum – stimulation of secretion of
large quantities of fluid with NaHCO3
• - Cholecystokinin – pancreozynin – duodenum – by way of the blood
to pancreas – causes secretion of quantities of the pancreatic
enzymes
• - Chymodenin – chymotrypsinogene
• - VIP – NaHCO3
Intestinal phase:

• Inhibitory influences:
• The presence of AA, fats ... secretion of GIP, VIP and secretion – GIT
hormones – blood –inhibition of the gastric secretion
• Drugs that influence gastric secretion
• Histamine – (H2 receptors) – cAMP
• Alcohol, coffeine
• ACTH – glucocorticoids – stimulate secretion of HCl and inhibit
secretion of mucus !!
 • In addition to neural stimuli, many hormonal factors also affect
peristalsis.

Those that increase intestinal motility;

Gastrin
Cholecystokinin
Insulin
Serotonin
Those that suppress intestinal motility;
Secretin
glucagon

19.03.2023 63
Hormones that inhibit gastric motility and emptying

• Vasoactive intestinal peptide (VIP)

• Gastric inhibitory peptide (GIP)
• Secretin
• Cholecystokinin
• Somatostatin
• Peptide YY

19.03.2023 64
 Hormonal
Control of GI
Motility
QUESTIONS..
Q1
• A 43-year-old man eats a meal consisting of 40 percent protein, 10
percent fat, and 50 percent carbohydrate. Thirty minutes later the
man feels the urge to defecate.
• Which reflex results in the urge to defecate when the duodenum is
stretched?
• A) Duodenocolic
• B) Enterogastric
• C) Intestino-intestinal
• D) Rectosphincteric
Q2
• A clinical experiment is conducted in which one group of subjects is
given 50 grams of glucose intravenously and another group is given
50 grams of glucose orally. Which factor can explain why the oral
glucose load is cleared from the blood at a faster rate compared with
the intravenous glucose load?
• A) CCK-induced insulin release
• B) CCK-induced vasoactive intestinal peptide (VIP) release
• C) GLP-induced glucagon release
• D) GLP-induced insulin release
• E) VIP-induced GLIP release
Q3
• The cephalic phase of gastric secretion accounts for about 30 percent
of the acid response to a meal. Which of the following can completely
eliminate the cephalic phase of gastric secretion?
• A) Antacids (e.g., Rolaids)
• B) Antigastrin antibody
• C) Atropine
• D) Histamine H2 blocker
• E) Vagotomy
Q4
• A 10-year-old boy consumes a glass of milk and two cookies. His LES
and fundus relax while the food is still in the esophagus. Which
substance is most likely to cause relaxation of the LES and fundus in
this boy?
• A. Gastrin
• B. Histamine
• C. Motilin
• D. Nitric oxide
• E. Norepinephrine
Q5
• An 89-year-old man has a cerebrovascular accident (stroke) in the
medulla and pons that completely eliminates all vagal output to the
gastrointestinal tract. Which function is most likely to be totally
eliminated in this man?
• A) Gastric acid secretion
• B) Gastrin release
• C) Pancreatic bicarbonate secretion
• D) Primary esophageal peristalsis
• E) Secondary esophageal peristalsis