Gastrointestinal Hormones

Overview of the GI Tract

Digestion and Absorption
Regulation of Digestive Functions
GI Hormones and Paracrine Factors
Integration of Neural and Endocrine Signals
Signaling Mechanisms

Functions of the GI Tract

Ingestion: Taking in food
Digestion: Chemical and Mechanical
Absorption: moving nutrients from the lumen of
the GI tract into the cells of the body
Excretion: getting rid of undigested and
unabsorbed material
Movement: movement of ingested food
throughout the GI tract

Organs of the Digestive System

Accessory Digestive Organs:
Salivary glands
Liver, gall bladder
Pancreas

Digestive Tract:
Oral Cavity
Pharynx
Esophagus
Stomach
Small Intestine
Large Intestine

The Oral Cavity

Boundaries are:
- lips (anteriorly)
- cheeks (laterally)
- palate (superiorly)
The oral cavity is important in:
- mastication (chewing): mechanical
digestion
- secretion of saliva for digestion (amylase;
digests starch), coating food (mucus)
- no significant absorption of nutrients occurs
in the oral cavity

The Pharynx
The pharynx is the passageway from the nose
and mouth to the esophagus and respiratory
tract
Boundaries: uvula to epiglottis
During swallowing, food is directed from pharynx
to esophagus (away from respiratory tract).

Esophagus
The esophagus is a passageway from the
pharynx to stomach
Contains two sphincters: upper and lower
esophageal sphincters (controls flow)
Upper sphincter is skeletal (voluntary), lower
sphincter is smooth muscle (involuntary)
Peristaltic waves move food from pharynx to
stomach.

The Stomach
The stomach stores food, and mixes and
mechanically and chemically digests it
The stomach also secretes digestive juices
pepsin: digests protein
hydrochloric acid (acidic pH, required for
pepsin activity, and to kill ingested bacteria)
Mucus: protects the stomach wall
Partially digested food: chyme
Little absorption occurs in the stomach
(exceptions: alcohol, aspirin)

Histology of the Stomach

Cell types:
Chief cells: produce pepsinogen (inactive
precursor to pepsin)
Parietal cells: produce HCl and intrinsic factor
(absorption of vitamin B12; important in RBC
maturation)
Endocrine cells:
G cells: gastrin
D cells: somatostatin (paracrine)
Enterochromaffin-like cells: histamine (paracrine)

Small Intestine
Connects the stomach with the large intestine
It is the major site of digestion
It is also the major site of absorption
Specialized structures (villi, microvilli) increase
the surface area of the small intestine, aiding
absorption.
The small intestine has three parts (duodenum,
jejunum, and ileum)
The bile duct (from liver) and pancreatic duct
(digestive juices) empty into the duodenum.

Histology of the Small Intestine

Absorptive cells
Goblet cells (mucus)
Enteroendocrine cells:
secretin
cholecystokinin

Digestion & Absorption: Carbohydrates

Carbohydrates: small amount of digestion begins in
oral cavity (amylase). Most digestion in small
intestine:
Enzyme
Digests
pancreatic amylase
polysaccharides to
disaccharides
disaccharidases
disaccharides into
(small intestine)
monosaccharides
Whats absorbed: monosaccharides

Digestion & Absorption: Proteins

Proteins: Digestion begins in stomach (pepsin),
continues in small intestine:
Enzyme
Digests
trypsin, chymotrypsin,
polypeptides into
carboxypeptidase
small peptides
(from pancreas)
aminopeptidase
dipeptidases
small peptides
into smaller
peptides

Whats absorbed: mono-, di-, and tri-peptides

Digestion & Absorption : Lipids

Lipids: Digestion begins in the small intestine (minor
amount in oral cavity)
Note: Lipids are not soluble in water. Thus, it is hard
for enzymes to act on them.
The first step in lipid digestion is emulsification of
lipids with bile (secreted from the liver).
Emulsification: transformation of large lipid
droplets into small lipid droplets.
This increases the surface area of lipid that can
be acted on by the digestive enzyme, pancreatic
lipase.

Emulsification of Lipids by Bile

Bile acts on lipids in a way similar to
detergent acting on greasy water:

large lipid droplet

bile
lipase

Absorption of Lipids
Bile also helps absorption of products of lipid
digestion, forming micelles (free fatty acids,
glycerol, cholesterol).
Absorption of lipids is required for absorption of
fat-soluble vitamins (vitamins A, D, E, K)

Digestion and Absorption: Nucleic Acids

Food also contains RNA and DNA (also from
shed cells of the GI tract).
The pancreas releases nucleases into the small
intestine.
Nucleases digest RNA and DNA into
components.
Digestion and absorption of dietary nucleic acids
probably not important for DNA/RNA synthesis.

Absorption in the Small Intestine: Water

About 9 liters of water enters the digestive tract
each day.
About 8 liters of this is absorbed by the small
intestine (by osmosis, following movement of
ions).

Large Intestine
Last portion of the digestive tract.
No digestion occurs in the large intestine.
In the large intestine, there is absorption of
water (about 1 liter/day) and salts from feces
(undigested, unabsorbed food).
Bacteria produce vitamin K, B vitamins.
Secretion of mucus (lubrication of feces)
Contractions move feces along large intestine
and rectum, to be expelled out of the anal
canal.

Accessory Digestive Organs

Pancreas: exocrine portion produces digestive
enzymes, bicarbonate
Liver: Produces bile, stores glycogen,
interconverts nutrients (gluconeogenesis),
detoxifies toxic substances (alcohol, drugs,
ammonia), makes blood proteins (albumin,
fibrinogen, clotting factors)
Gallbladder: concentrates and stores bile

Regulation of Digestion
Allow communication between different parts of
the digestive tract
Ensure the presence of sufficient secretions
when food present
Help avoid overabundance of secretions in
absence of food
Two types of mechanisms: neural and endocrine

Neural Control of Digestion

Neural control of digestion is controlled largely by the
parasympathetic nervous system, and local (enteric) reflexes.
Activation of the parasympathetic system results in secretion
of digestive juices, increased motility of the stomach, and
slowing down movement of food from the stomach to small
intestine.
Stimuli: Thought, sight, taste of smell of food; distension of GI
tract; chemoreceptors detecting nutrients, pH.
Example: Thought, chewing, or taste of food activates
parasympathetic system, resulting in increased release of
mucus, HCl, and pepsin in the stomach.
The goal of this is to prepare the stomach for oncoming food.

Intestinal Phase of Gastric Secretion

(~ 10% of total)
(due to some G cells extending from
antrum into the duodenum)

Important aspect of intestinal phase is feedback

regulation and inhibition
Involves interactions between duodenal contents
and duodenal hormones, including their actions
on pancreas, liver, gall bladder, and stomach

B. Functional Phases of Gastric Secretion

2. Gastric Phase of

1. Cephalic Phase of

Gastric Secretion (approx.

30% of total)

Gastric Secretion
(approx 60% of total)

(initiated by brain)

(initiated by gastric events)

vagus
nerve

vagus
nerve

FOOD
HCl

HCl

Distension
Peptides
circulation

gastrin

circulation

gastrin

C. G.I. HORMONES

+
+
+
+
+

H+
psnogn
motil.
LES
growth

+
+
+
-

Gastrin (17 AA)

HCO3 output
psnogn
synrg w/ CCK
gastr emptying
H+

Cholecystokinin (CCK (33 AA))

+
+
+
-

Structure of Secretin (27 AA)

(comparison with other GI hormones)

panc enz
G.B.
growth
Oddi
gastr emptying
synrg w/ Secretin

Endocrine Control of Digestion

Gastrin:
- produced from the stomach (G cells)
- release increased by stomach
distension, peptides, amino acids, alcohol,
caffeine, parasympathetic innervation
- release inhibited by highly acidic pH
(< 2.0)
- functions: increases gastric (stomach)
secretions (primarily HCl); increases
histamine release; increases gastric motility;
opens pyloric sphincter (between stomach
and small intestine), relaxes ileocecal
sphincter, stimulates growth of gastric
mucosa.

Endocrine Control of Digestion

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).

HOW IT WORKS AT THE RECEPTOR LEVEL

Combined neurocrine, endocrine and paracrine

events in the activation of gastric HCl secretion

Acetylcholine
neural input
neurocrine

ACh
receptor

PARIETAL cell

histamine
receptor

H/K
P

ECL cell

transductionactivation events

histaminesecreting cell

H/K
P

HCl
secretion

gastrin
receptor

Gastrin
hormonal input
endocrine

paracrine
release of
histamine

circulation

G cell

ECL cell =
enterochromaffin-like cell
t
l inpu
a
r
u
e
n

chemical input

G cell =
gastrin-secreting cell

HOW IT WORKS AT THE RECEPTOR LEVEL

Combined neurocrine, endocrine and paracrine

events in the activation of gastric HCl secretion

Acetylcholine
neural input
neurocrine

ACh
receptor

PARIETAL cell

histamine
receptor

H/K
P

ECL cell

HCl

transductionactivation events

histaminesecreting cell

secretion

H/K
P
gastrin
receptor

Gastrin
hormonal input
endocrine

paracrine
release of
histamine

circulation

G cell

H-2 receptor blockers

Tagamet
ECL cell =
Zantac
enterochromaffin-like
cell
Pepcid
t
l inpu
a
r
u
e
n

chemical input

H/K ATPase pump inhibitors

G cell =
Prilosec
gastrin-secreting cell
Nexium
Aciphex

Turning the G-cell On

and Off
vagus
nerve

ACh

gastric
mucosa

ACh

ACh

GRP +

(Somatostatin)

cell

+
H+

Gastric Lumen

GRP
neuron

cholinergic
neuron

SS

(Gastrin)

cell

+
digested
protein

Gastric Lumen

Circulating
Gastrin

Turning the G-cell On

and Off
vagus
nerve

ACh

gastric
mucosa

ACh

GRP +

ACh

(Somatostatin)

cell

Gastric Lumen

GRP
neuron

cholinergic
neuron

Circulating
Gastrin

SS

(Gastrin)

cell

+
digested
protein

SS = somatostatin

Endocrine Control of Digestion

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.
Actions: inhibit gastrin and histamine secretion
(decreased acid release and gastric motility); also
directly inhibits acid release from parietal cells.

Endocrine Control of Digestion

Secretin:
- Produced by duodenum (enteroendocrine cells
of the small intestine); crypts of Lieberkhn
- stimulated by arrival of acidic chyme in
duodenum.
- functions: stimulates bicarbonate secretion
from pancreas; inhibits gastric secretion
(decreases HCl production by inhibiting gastrin
release); decreases gastric motility (slowing
rate of gastric digestion and delivery to the
small intestine), increases hepatic bile
production, increases CCK, promotes growth
and maintenance of the pancreas.

Endocrine Control of Digestion

Cholecystokinin (CCK):
- produced by enteroendocrine cells of the
duodenum
- release stimulated by fatty acids in
duodenum (also amino acids, acidic chyme)
- functions: causes gallbladder contraction
(bile to small intestine); stimulates release of
pancreatic enzymes; decreases gastric
motility and secretion (increases somatostatin
release).

Endocrine Control of Digestion

Gastric Inhibitory Peptide (GIP):
Secretion: Enteroendocrine cells in the small
intestine mucosa Crypts of Lieberkuhn
Stimulus: Chyme rich in triglycerides, fatty acids,
and glucose enter the small intestine.
Actions:

Stimulates release of insulin by beta cells

Inhibits gastric secretion and motility
Stimulates lipogenesis by adipose tissue
Stimulates glucose use by skeletal muscle cells

Endocrine Control of Digestion

Vasoactive Intestinal Peptide (VIP):
Secretion: Enteroendocrine cells in the small
intestine mucosa Crypts of Lieberkuhn
Stimulus: Chyme entering the small intestine.
Actions:
Stimulates buffer secretion
Inhibits gastric secretion
Dilates intestinal capillaries

Control of Gastric Acid Secretion

How does a parietal cell secrete hydrochloric
acid?
H+
Cl-

CO2 + H20

H2CO3

H+ + HCO3-

HCO3- Cl-

Control of Gastric Acid Secretion

D Cell

CCK
SECRETIN

somatostatin (-)

G Cell
Gastrin

ECL

histamine

HCl

parietal
cell

Integration of Neural and Endocrine

Functions: Central Effects
CNS: Thoughts, taste, smell of food; chewing
activates parasympathetic nervous system
(neurotransmitter: acetylcholine).
ACh acts directly on parietal cells to increase
acid secretion.
Ach increases gastrin release, inhibits
somatostatin release (increased gastric
secretion and motility).
Sympathetic input (activity, stress): increased
somatostatin release (inhibiting gastrin secretion
decreased gastric secretion and motility)

Integration of Neural and Endocrine

Functions
Vagus N.
ACh

(-)
D Cell

CCK
SECRETIN

somatostatin (-)

G Cell
Gastrin
(+)
Digested protein

ECL

histamine

(+)

(+)

HCl

parietal
cell

Integration of Neural and Endocrine

Functions: Local Reflexes
Mechanoreceptors in the walls of the GI tract detect
movement of food into an organ
Example: In the stomach distension causes
activation of the parasympathetic system,
increasing gastrin secretion and acid release, and
decreasing somatostatin secretion.
Chemoreceptors detect nutrients and pH.
Example: Presence of amino acids, alcohol, or
caffeine in the stomach increases gastrin release.
Presence of fatty acids in the duodenum causes
release of CCK.

Signaling Mechanisms
Histamine: Receptor coupled to Gs increases
cyclic AMP production and acts via PKA.
Results in phosphorylation and increased
transport of proton pumps to cell membrane.
Gastrin: Receptor coupled to Go/IP3/DAG;
increased intracellular calcium, and activation of
PKC (PKC also phosphorylates proton pumps).
Somatostatin: Receptor coupled to Gi inhibits
cyclic AMP production, decreasing PKA
signaling.

Signaling Mechanisms
CCK: Receptor coupled to Go (increased
calcium causes somatostatin release)
Secretin: Receptor couple to Gs (increased
cyclic AMP, causes increased secretion of
bicarbonate from the pancreas)

Integration of Gastric Secretion

+
+

Integration of Gastric Secretion

+
+

D. Duodenal Integration & Control:

1. Response to Acidity

Regulation by Secretin
liver

HCO3

C
H
Na

gall
bladder
ti n
e
cr
e
S

NaCl
+ H2O

N
aH
C

O3

+
-

HCl
motility

HCl
O

+ HCl

HCl+NaHCO3NaCl+CO2+H2O

2. Duodenal Response to Food

Regulation by CCK (Cholecystokinin)

liver

Bile
gall

bladder

K
C
C
fat &
protein
digestion

bile &
enzymes

fats &
peptides

- HCl

FOOD