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Gastrointestinal Hormones ( Enteric Hormones)
Hormones secreted by the gastrointestinal mucosal epithelial cells, lining the lumen of the
stomach, small intestine and the colon. These hormone‐secreting cells are called
endocrinocytes
It regulate the secretion of digestive enzymes and the motor activity of the digestive
system
Categories
1‐ Gastrin
Synthesized in G cells, which are located in gastric pits, primarily in the antrum region of
the stomach.
¾ It Stimulates gastric acid secretion by binding receptors found predominantly on parietal
and enterochromaffin‐like cells (leads to histamine release from enterochromaffin cells,
which binds to H2 receptors on parietal cells which is necessary for acid secretion).
¾ It also has an important trophic influence on the gastric mucosa.
The primary stimulus for secretion of gastrin is presence of peptides, certain amino acids
and calcium in the gastric lumen
Also, unidentified compounds in coffee, wine and beer are potent stimulants for gastrin
secretion
Secretion of this hormone is inhibited when the lumenal pH of the stomach becomes very
low (less than 3).
Excessive secretion of gastrin, or hypergastrinemia, is a well‐recognized cause of Zollinger‐
Ellison syndrome,
Most commonly, hypergastrinemia is the result of gastrin‐secreting tumors (gastrinomas),
which develop in the pancreas or duodenum.
2‐ Cholecystokinin
It is secreted from mucosal epithelial cells in the first segment of the small intestine
(duodenum), Cholecystokinin is also produced by neurons in the nervous system, and is
widely distributed in the brain.
The most potent stimuli for secretion of cholecystokinin are the presence of partially‐
digested fats (triglyceride) and proteins in the lumen of the duodenum, also
polysaccharides play role.
It Stimulates secretion of pancreatic enzymes, and contraction and emptying of the gall
bladder needed for their digestion.
Cholecystokinin may be the mediator of satiety.
Diseases resulting from excessive or deficient secretion of cholecystokinin are rare.
Cholecystokinin deficiency has been described as part of autoimmune polyglandular
syndrome, and manifest as a malabsorption syndrome.
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3‐ Secretin:
It is secreted from mucosal epithelial cells in the first part of the small intestine.
It is released in response to acid in the small intestine (acidification of the duodenum), and
Stimulates secretion of water and bicarbonate from the pancreas (principal target) and bile
ducts (2ndry target), which neutralizes the acid.
4‐ Gastric inhibitory polypeptide (GIP)
Is a member of the secretin family, it is produced by enteroendocrine K‐cells, which are
found in highest numbers in the duodenal and jejunal epithelia. It is released in response
to presence of fat and glucose in the small intestine
Inhibits gastric motility and potentiates release of insulin from beta cells in response to
elevated blood glucose concentration.
5‐ Ghrelin
Primarily it is secreted from the stomach, but also in smaller amounts from the intestine.
The hypothalamus in the brain is another significant source of ghrelin; also smaller
amounts are produced in the placenta, kidney, and pituitary gland.
Action:
¾ It stimulate secretion of growth hormone through cells within the anterior pituitary that
bear it receptors. these receptors named the growth hormone secretagogue receptor
(GHS‐R).
The ghrelin signal is integrated with that of growth hormone releasing hormone and
somatostatin to control the timing and magnitude of growth hormone secretion.
¾ Regulation of energy balance, it has a strong stimulant for appetite and feeding; and
increase hunger through receptors in the hypothalamus long known to be involved in
appetite regulation.
Ghrelin concentrations in blood are reduced in obese humans compared to lean humans
¾ In Prader‐Willi syndrome affected patients develop extreme obesity associated with
uncontrollable and voracious appetite. The plasma ghrelin levels are exceptionally high
in comparison to patients similarly obese (low levels) due to other causes. So excessive
ghrelin production may contributes to the appetite and obesity components of Prader‐
Willi syndrome.
6‐ Motilin
Controls the pattern of smooth muscle contractions in the upper gastrointestinal tract
(stomach and small intestine).
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Motilin is secreted into the circulation during the fasting state at intervals of roughly 100
minutes after meals.
These bursts of motilin secretion sweep the stomach and small intestine clear of
undigested material.
Erythromycin and related antibiotics act as nonpeptide motilin agonists, and are
sometimes used for their ability to stimulate gastrointestinal motility.
7‐ Enteroglucagon and Glucagon‐Like Peptides
A‐ Glucagon is best known as a peptide hormone secreted within alpha cells of the
pancreatic islets that express the proglucagon gene.
It participates in control of glucose metabolism, and it action was discussed in DM lectures.
The proglucagon gene is also expressed in the terminal small intestine and large intestine,
where it is cleaved into a number of peptides other than glucagon in endocrinocytes called
L cells.
These peptides were discovered by cross reactions with antisera against glucagon, they
were originally given the name "enteroglucagon", now many types were identified:
Glucagon‐like peptide‐1 (GLP‐1),
other types of "enteroglucagon" with less activity, are
Glucagon‐like peptide‐2 (GLP‐2),
Oxyntomodulin,
And glicentin.
All are secreted into blood after ingestion of a meal containing carbohydrates or lipids.
B‐ Glucagon‐like peptide‐1 is a product of alternative processing of proglucagon in
enteroendocrine L‐cells, which are found along the length of the intestinal tract but at
highest density in the distal ileum and colon.
Has a major effect of enhancing the release of insulin in response to a glucose stimulus,
and suppress secretion of glucagon so lower blood glucose levels.
Also GLP‐1 has been shown to inhibit gastric emptying, gastric secretion and pancreatic
secretion.
GLP‐1 is also synthesized in the brain, and may play a role in control of food intake
(decrease appetite).
8‐ Vasoactive Intestinal Peptide (VIP)
Discussed
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ﻓﺎروق
اﻟﻌﺰاوي
2014/2015