Chapter 7
Gastrointestinal Hormones
Nam Deuk Kim, Ph.D.
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Digestive System
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1. Gastrointestinal Tract Structure and Function
Summary of
Pathways
Controlling
Digestive
System
Activities
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Gastrointestinal
Secretions
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Enterohepatic circulation of Control of the ileocecal
bile salts valve/sphincter
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Major Gastrointestinal Hormones
• Gastrin
– Release is stimulated by presence of protein in
stomach
– Secretion inhibited by accumulation of acid in stomach
– Functions
• Acts in several ways to increase secretion of HCl and
pepsinogen
• Enhances gastric motility, stimulates ileal motility, relaxes
ileocecal sphincter, induces mass movements in colon
• Helps maintain well-developed, functionally viable digestive
tract lining
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• Secretin
– Presence of acid in duodenum stimulates release
– Functions
• Inhibits gastric emptying in order to prevent further acid from
entering duodenum until acid already present is neutralized
• Inhibits gastric secretion to reduce amount of acid being
produced
• Stimulates pancreatic duct cells to produce large volume of
aqueous NaHCO3 secretion
• Stimulates liver to secrete NaCO3 rich bile which assists in
neutralization process
• Along with CCK, is trophic to exocrine pancreas
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• Cholecystokinin (CCK)
– Functions
• Inhibits gastric motility and secretion
• Stimulates pancreatic acinar cells to increase secretion of
pancreatic enzymes
• Causes contraction of gallbladder and relaxation of sphincter
of Oddi
• Along with secretin, is trophic to exocrine pancreas
• Implicated in long-term adaptive changes in proportion of
pancreatic enzymes in response to prolonged diet changes
• Important regulator of food intake
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• Gastric inhibitory peptide (GIP)
– Inhibitory effects on gastric acid secretion
– Glucose-dependent insulinotrophic peptide
– Stimulates insulin release by pancreas
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Gastric secretion gradually decreases as food
empties from the stomach into the intestine.
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Hormonal control of pancreatic secretion
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2. Source and Chemistry of the
Gastrointestinal Hormones
• The GI hormones are synthesized within a system of
clear cells (enterochromaffin, argyrophil, or argentaffin
cells), so called because they are selectively stained by
certain silver salts.
• These clear cells, scattered within the GI tract mucosa
from the stomach through the colon, are often referred to
as the diffuse or dispersed endocrine system, or, along
with the pancreatic hormones, as the
gastroenteropancreatic hormones.
• Enterochromaffin-like (ECL) cells
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1) Gastrin hormone family members contain a biologically
active C-terminal pentapeptide sequence
Fig. 10-1: Amino acid sequences of human G-17 gastrin and
cholecystokinin (CCK). Identical C-terminal pentapeptide
sequences are indicated.
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Fig. 10-2: Structure of pentagastrin.
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2) Secretin shares partial sequence identity with glucagon, GIP
and VIP
Fig. 10-3: Amino acid sequences of porcine peptides of the
secretin family. Boxed areas indicate identical amino acid
sequences between peptides.
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3) The GI tract produces other biologically active peptides that
are putative hormones
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3. Physiological Roles of the Gastrointestinal Hormones
Fig. 10-4: Schematic drawing indicating the possible actions of enteroendocrine cells. The
stimulus from the intestinal lumen acts on the receptors of the brush-border membrane,
resulting in a release of hormones by exocytosis. The peptide hormones may exert their effect
on the following: (a) adjacent epithelial cells, nerve fibers, nerve cells, smooth muscle, and
connective tissue cells of the lamina propria; (b) cells of the whole organism following delivery to
the systematic circulation. Method (a) is described as paracrine; method (b) is referred to19as
endocrine.
1) Gastrin stimulates acid secretion in the stomach
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Fig. 10-5: Neuroendocrine integration of gastric acid secretion. (See also Fig. 10.14.)
2) Secretin stimulates pancreatic bicarbonate and enzyme secretions
Hormonal control of pancreatic secretion
Fig. 10-6: Homeostatic closed-loop endocrine mechanism of small intestine pH control.
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3) CCK stimulates gallbladder contraction and pancreatic
enzyme secretions
Fig. 10-7: Plasma cholecystokinin (CCK) responses to a meal in normal subjects and
patients with bulimia (uncontrollable eating). After an overnight fast, 14 patients with
bulimia and 10 age- and sex-matched normal volunteers were fed a 400 ml mixed-
liquid meal. Plasma was collected and extracted at the indicated times and assayed
for CCK bioactivity, expressed as cholecystokinin-8 equivalents. Values are means ±
SEM. The arrow indicates the beginning of the meal. 22
4) Gastric inhibitory peptide (GIP) inhibits gastric emptying and
gastric acid secretion.
• 43-aa peptide
• Inhibitory effects on gastric acid secretion
• Glucose-dependent insulinotrophic peptide
• Stimulates insulin release by pancreas
5) Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion and
inhibits glucagon secretion
6) Vasoactive intestinal peptide (VIP) inhibits gastric acid secretion
and stimulates pancreatic electrolyte and water secretion
7) Neurotensin stimulates pancreatic secretion and inhibits gasrtic
motility.
8) Peptide YY inhibits pancreatic bicarbonate secretion, gallbladder
contraction, and gastric emptying.
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9) Substance P (SP) may serve as a physiological modulator of
intestinal smooth muscle contractility.
10) Somatostain inhibits gastrin and hydrochloric acid release.
11) Gastrin-releasing peptide (GRP) stimulates release of several GI
hormones, pancreatic secretion, and motility.
12) Motilin stimulates GI motility and emptying of chyme into the
small intestine.
13) Ghrelin is a multifunctional peptide that stimulates gastric acid
secretion and gastric motility.
14) Other putative gut hormones exert specific actions in the GI tract.
• Urogastrone/EGF
• Villikinin
• Enkephalins
• Hormones in milk
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Fig. 10-9: Schematic drawing
showing a three-dimensional
arrangement of the somatostatin
cells and their processes in an
antral gland.
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Fig. 10-10: Primary structures of bombesin and porcine
gastrin-releasing peptide (GRP).
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Fig. 10-11: Amino acid sequence of human -urogastrone.
Positional amino acid differences between -urogastrone
and mouse EGF are shown in parentheses.
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4. Gastrointestinal Hormone Mechanisms of Action
1) Integrated actions of gastrin, acetylcholine, and
histamine control gastric acid secretion
Fig. 10-12: This diagram represents the interaction of the gastrin, enterochromaffin-like (ECL), parietal, and
somatostatin cells. Both antral and fundic somatostatin cells appear to exert inhibitory influences on gastrin,
ECL, and parietal cells, respectively. Neurotransmitter substances from either the vagus or the intrinsic gastric
neural system are responsible for modulation of each of the cells and their secretory activity. Luminal amino
acids stimulate gastrin release, whereas luminal protons inhibit gastrin release. Systemic secretion of gastrin
primarily drives ECL cells to secrete histamine but may play some part in parietal cell secretion, although a
trophic regulatory effect is more likely. The ECL cells release histamine, which presumably functions 28in a
paracrine fashion to stimulate parietal cell secretion. Inhibitory actions of hormones are noted (–).
2) Synergistic actions of secretin and CCK control
exocrine pancreatic secretion
Fig. 10-13: Hypothetical model for the synergistic actions of
CCK and secretin (S) and second messengers on pancreatic
enzyme and bicarbonate secretion.
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5. Summary of the Neuroendocrine Control of GI Function
Fig. 10-14: Summary scheme of hormone-metabolite control of GI
function. Solid lines indicate stimulatory influences; dashed lines
represent inhibitory stimuli.
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6. Pathophysiology
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