GASTROINTESTINAL HORMONES

By

N. M. Gidado, Ph.D

June, 2024.
 INTRODUCTION
➢ Local hormones are polypeptides in nature
secreted by the GI tract to regulate its movements
and secretory activities.

❑ Enteroendocrine Cells
➢ Hormone-secreting cells in the form of nerve and
glandular cells present in the gastric and intestinal
mucosa as well as the pancreas.
➢ Enteroendocrine cells which secrete hormones
from amines are called neuroendocrine or amine
precursor uptake and decarboxylation (APUD) cells.
✓ Meaning, a precursor substance of an amine is
taken up first by the cells & later decarboxylated to
form the amine required for hormone synthesis.
✓ Enteroendocrine cells which secrete serotonin and
histamine are referred to as enterochromaffin and
enterochromaffin-like cells, respectively.
 GASTRIN
➢ A peptide hormone with 34 AA residues secreted
mainly by G cells & islets of Langerhans in fetus.
➢ Stimulants for secretion of gastrin include;
i. Food presence in the stomach,
ii. Stimulation of local nerve plexus,
iii. Vagovagal reflex via GRP by vagal n. endings.
➢ Actions of gastrin include;
i. Stimulation of pancreatic & gastric juice secretion,
ii. Accelerates gastric motility,
iii. Promote growth of gastric mucosa,
iv. Stimulates the release of pancreatic hormones by
islets of Langerhans,
 SECRETIN
➢ A peptide hormone with 27 amino acid residues.
secreted by the S cells of small intestine.
➢ Produced at first in an inactive form ‘prosecretin’
then converted into secretin by acidity of chyme.
➢ Acid chyme and products of protein digestion
stimulate the release of prosecretin.
➢ Actions of secretin include;
i. Stimulation of pancreatic juice secretion,
ii. Inhibits gastric juice secretion and motility,
iii. Causes constriction of pyloric sphincter,
iv. Increases CCK potency on pancreatic secretion.
 CHOLECYSTOKININ PANCREOZYMIN (CCK-PZ)
➢ A peptide hormone with 39 AA residues secreted
mainly by I cells in mucosa of small intestine.
➢ Stimulants for secretion of CCK-PZ is the presence
of chyme containing digestive end products of fats
& proteins in the duodenum. Its actions include;
i. Stimulation of pancreatic juice secretion,
ii. Stimulates gallbladder contraction,
iii. Augments secretin activity & enterokinase secret.,
iv. Inhibits gastric but increases intestinal motilities,
v. Augments contraction of pyloric sphincter,
vi. Plays a vital role in satiety by suppressing hunger,
vii. Induces drug tolerance to opioids.
 GLUCOSE-DEPENDENT
INSULINOTROPIC HORMONE
➢ Formerly gastric inhibitory peptide (GIP) made up
of 42 amino acid residues secreted by K cells in
antral & intestinal mucosa.
➢ Its secretion is stimulated by entry of chyme
containing glucose and fat into the duodenum.
➢ Actions of Gastric inhibitory peptide include;
i. Stimulates insulin secretion thus, called glucose-
dependent insulinotropic hormone,
ii. Mild inhibition of gastric juice secretion,
iii. Inhibits gastric motility.
 VASOACTIVE INTESTINAL POLYPEPTIDE (VIP)
➢ A polypeptide hormone with 28 AA residues
secreted in stomach, small & large intestines. Acid
chyme is the major stimulant for its secretion.
➢ Actions of VIP include;
i. Dilates splanchnic (peripheral) blood vessels,
ii. Inhibits HCl secretion in gastric juice,
iii. Stimulates small intestinal juice secretion,
iv. Relaxes intestinal smooth muscles,
v. Stimulates insulin secretion.
vi. Augments action of acetylcholine on salivary
glands.
 GLUCAGON
➢ A polypeptide hormone with 29 AA residues
secreted mainly by alpha or A cells of islets of
Langerhans in pancreas & stomach.
➢ It is also secreted by L cells in the intestine as
preproglucagon. Stimuli for its secretion include;
i. Presence of fatty & proteineous meal in
stomach stimulates glucagon secretion in
stomach & duodenum.
ii. Hypoglycemia stimulates pancreatic secretion
of glucagon.
➢ Overall action of Glucagon is to increase blood
glucose level.
 GLICENTIN
➢ A polypeptide secreted majorly by L cells in small
intestine and α-cells of pancreatic islets.
➢ It is secreted as preproglucagon converted in the;
i. Intestine into glicentin and glucagon-like
polypeptide-2 (GLP-2),
ii. Pancreas into glucagon and GLP-1, and other
proglucagon fragments.
➢ Presence of fatty and/or proteineous chyme in the
intestine stimulates Glicentin secretion.
➢ Glicentin show actions similar to those of glucagon.
The overall effect is increase in blood glucose level.
 GLUCAGON-LIKE POLYPEPTIDE 1 & 2 (GLP-1 & 2)
➢ GLP-1 is secreted in α-cells of pancreatic islets
structurally similar to GLP-2 (secreted by L cells in
intestine) and glucagon.
➢ Presence of food with glucose in the small intestine
stimulates the release of both GLP-1 & GLP-2.
➢ Actions of GLP-1 include;
i. Stimulates the insulin secretion from β-cells,
ii. Inhibits gastric motility.
➢ Actions of GLP-2 include;
i. Overall action of GLP-2 is that it is believed to
be a potent appetite suppressor.
 SOMATOSTATIN
➢ A peptide hormone secreted in two forms, one
with 14 AA & the other 28 AA found in D cells of
islets, stomach & duodenum.
➢ Presence of chyme containing glucose and proteins
in stomach & small intestine stimulates its release.
➢ Actions of Somatostatin include;
i. Inhibits GH and TSH secretions,
ii. Inhibits gastric secretion and motility,
iii. Inhibits secretion of pancreatic juice,
iv. Inhibits secretion of GI hormones such as Gastrin,
CCK-PZ, VIP and GIP.
 PANCREATIC POLYPEPTIDE
➢ A polypeptide with 36 AA residues secreted mainly
by the PP cells of islets of Langerhans and is also
found in small intestine.
➢ Its secretion is triggered by presence of chyme with
proteins in small intestine and as well in some
conditions like hypoglycemia, fasting and exercise.
➢ Actions of pancreatic polypeptide include;
i. Increases glucagon secretion from α-cells of
islets of Langerhans in pancreas.
ii. Decreases pancreatic juice secretion from
exocrine portion of pancreas.
 POLYPEPTIDE YY OR PEPTIDE YY
➢ Polypeptide with 36 AA residues secreted in the L
cell of ileum & colon, but structurally related to
pancreatic polypeptide & neuropeptide Y.
➢ Its secretion is triggered by presence of chyme
containing fat in the intestine.
➢ Actions of peptide YY include;
i. Inhibition of gastric secretion and motility,
ii. Reduces pancreatic juice secretion,
iii. Inhibition of intestinal motility which stops the
passage of bowel beyond ileum (ileal brake),
iv. Suppresses appetite and food intake.
 NEUROPEPTIDE Y
➢ A polypeptide containing 36 AA residues secreted
by enteric nerve endings in small & large intestines,
& in medulla, hypothalamus & ANS neurons.
➢ It is structurally related to pancreatic polypeptide
and peptide YY. Secretion is triggered by chyme
containing fat.
➢ Actions of neuropeptide Y include;
i. Increases the blood flow in enteric blood
vessels,
ii. Stimulates food intake.
 MOTILIN
➢ A polypeptide made up of 22 AA residues secreted
by Mo cells present in stomach and intestine, & in
small amounts by enterochromaffin cells.
➢ Its secretion is triggered by entry of acid chyme
into the duodenum.
➢ Actions of Motilin include;
i. Accelerates gastric emptying,
ii. Increases both mixing & propulsive movements
of small intestine,
iii. Increases the peristaltic contractions of large
intestine.
 SUBSTANCE P
➢ A neurotransmitter with 11 AA residues secreted at
the pain nerve endings in the brain and enteric
nerve endings in small intestine.
➢ Secretion of substance P in intestine is stimulated
by the presence of chyme in the intestine.
➢ Actions of substance P in the GI tract include;
i. increases mixing movements of small intestine,
ii. Increases propulsive movements of small
intestine.
 GHRELIN
➢ A polypeptide hormone with 28 AA residues
synthesized by epithelial cells in the gastric fundus.
➢ It is also synthesized in small amounts by the
hypothalamus, pituitary, kidney and placenta.
➢ Hunger is the major stimulus for its secretion thus,
increases during fasting & decreases when stomach
is full. Actions of Ghrelin include;
i. Promotes secretion of growth hormone (GH),
ii. Stimulates gastric emptying,
iii. Induces appetite and food intake by stimulating
the feeding center in hypothalamus.
 OTHER GASTROINTESTINAL HORMONES
❑ GIT mucosa also secretes many other hormonal
substance such as;
i. Enkephalins, vi. Enterocrinin,
ii. Dynorphin, vii. Villikinin,
iii. Neurotensin, viii.Guanylin, and
iv. Serotonin, ix. Bombesin.
v. Urogastrone,

However, physiological actions of some of these