Gastrointestinal GI Hormones

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Gastrointestinal (GI) Hormones Gastrin and
ZES CCK Secretin Gherelin Motilin

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Motilin Motilin is a 22 aa peptide secreted by
endocrinocytes (mo cells) in the mucosa of the
proximal SI. Based on aa sequence, motilin is
unrelated to other hormones. Motilin
participates in controlling the pattern of smooth
muscle contractions in the upper GI tract.

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Motilin There are two basic states of motility
of the stomach and SI the fed state, when
foodstuffs are present and the interdigestive
state between meals. Motilin is secreted into
the circulation during the fasted state at
intervals of roughly 100 minutes. These bursts
of motilin secretion are temporily related to the
onset of "housekeeping contractions", which sweep
the stomach and SI clear of undigested material.

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Motilin is secreted by Mo cells of the SI that
increases the MIGRATING MYOELECTRIC COMPLEX
component of GI motility and stimulates the
production of PEPSIN. Control of motilin
secretion is largely unknown, although some
studies show that alkaline pH in the duodenum
stimulates its release. Interestingly however,
at low pH it inhibits gastric motor activity,
whereas at high pH it has a stimulatory
effect. Apart from in humans, motilin receptors
are found in pigs', rats',cows' and cats'
gastrointestinal tracts and in rabbits' central
nervous systems.

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Motilin An interesting aspect of the motilin
story is that erythromycin and related
antibiotics act as non-peptide motilin agonists,
and are sometimes used for their ability to
stimulate GI motility. Administration of a low
dose of erythromycin will induce a migrating
motor complex, which provides additional support
for the conclusion that motilin secretion
triggers this pattern of GI motility, rather than
results from it.

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Motilin Most recently, an orphan GPCR related
to growth hormone secretagogues receptor (GHS-R)
has been isolated and characterized from human
stomach as the motilin receptor (MTLR or GPR38
52 identity with GHS-R). Polymorphisms of the
motilin gene in inflammatory bowel disease.

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Gastric Inhibitory Peptide Gastric inhibitory
peptide (GIP) is a member of the secretin family
of hormones. It was discovered as a factor in
extracts of intestine that inhibited gastric
motility and secretion of acid, and initially
called enterogastrone. Like secretin, it is
secreted from mucosal epithelial cells in the
first part of the small intestine. Another
activity of GIP is its ability to enhance the
release of insulin in response to infusions of
glucose. For this action, it has also been
referred to as glucose-dependent insulinotropic
peptide.

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• Vasoactive Intestinal Peptide
• VIP is a 28 aa peptide structurally related to
  secretin.
• originally isolated from intestinal extracts and
  shown to be a potent vasodilator.
• demonstrated that VIP is very widely distributed
  in the peripheral and CNS

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• Vasoactive Intestinal Peptide
• A huge of biological effects have been
  attributed to VIP.
• With respect to the digestive system, VIP seems
  to induce smooth muscle relaxation (lower
  esophageal sphincter, stomach, gallbladder),
  stimulate secretion of water into pancreatic
  juice and bile, and cause inhibition of gastric
  acid secretion and absorption from the intestinal
  lumen.

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Vasoactive Intestinal Peptide Certain tumors
arising from the pancreatic islets or nervous
tissue (called VIPomas) secrete excessive
quantities of VIP, and are associated with
chronic, watery diarrhea.

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Enteroglucagon and Glucagon-Like
Peptides Glucagon is best known as a peptide
hormone secreted from pancreatic islets and
participates in control of glucose metabolism.
Glucagon is synthesized initially as the
protein proglucagon, which, in mammals, is
encoded by a single gene. Within alpha cells of
the pancreas, proglucagon is processed by
proteolytic cleavage into glucagon itself, and
several biologically inactive peptides.

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Enteroglucagon and Glucagon-Like Peptides
Interestingly, the proglucagon gene is also
expressed in the terminal SI and LI, where it is
cleaved into a number of peptides other than
glucagon. This alternative pathway for
processing of proglucagon occurs in gut
endocrinocytes called L cells. Because these
peptides were discovered by cross reactions with
antisera against glucagon, they were originally
given the name "enteroglucagon", and are
sometimes referred to collectively as
"proglucagon-derived peptides".

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Enteroglucagon and Glucagon-Like Peptides The
major, characterized patterns of proglucagon
processing are depicted in the next few slides.
In both pancreas and gut, 3 types of products
are generated Peptides with known biological
activity (yellow color) glucagon and
glucagon-like peptide-1 (GLP-1)

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Enteroglucagon and Glucagon-Like Peptides
Peptides that may have biological activity, but
which are poorly characterized or active only at
what are considered non-physiologic
concentrations (cyan color) glucagon-like
peptide-2 (GLP-2) and oxyntomodulinPeptides
without apparent biological activity (gray
color) glicentin, glicentin-related pancreatic
peptide, major proglucagon fragment.

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Regardless of activity, each of these peptides is
secreted into blood after ingestion of a meal
containing carbohydrates or lipids.

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Glucagon-like peptide-1 has a major effect of
enhancing the release of insulin in response to a
glucose stimulus, and coincidentally, suppressing
secretion of glucagon. As a result, injections of
this hormone lower blood glucose levels, not only
in normal people, but in those having
insulin-dependent and NIDDM. For this reason,
GLP-1 is being used in diabetes therapy.

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GLP-1 has been shown to potently inhibit several
aspects of digestive function, including gastric
emptying, gastric secretion and pancreatic
secretion. Like many gut peptides, GLP-1 is
also synthesized in the brain, and may play a
role in control of food intake

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Glucagon-like peptide-2 is not well
characterized, but some reports suggest that it
stimulates proliferation of intestinal epithelial
cells.

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Oxyntomodulin is identical to glucagon, but
with an 8 amino acid extension on the C-terminus.
Experimentally, it has glucagon-like activity,
but this is of doubtful physiologic significance,
as it binds the glucagon receptor with low
affinity relative to glucagon. Other effects
that have been demonstrated include inhibition of
gastric secretion and motility, and inhibition of
pancreatic secretion.

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The Enteric Nervous System The nervous system
exerts a profound influence on all digestive
processes, namely motility, ion transport
associated with secretion and absorption, and GI
blood flow. Some of this control emanates from
connections between the digestive system and CNS,
but just as importantly, the digestive system is
endowed with its own, local nervous system
referred to as the enteric or intrinsic nervous
system. The magnitude and complexity of the
enteric nervous system is immense - it contains
as many neurons as the spinal cord.

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The Enteric Nervous System The principal
components of the enteric nervous system are 2
networks (or plexuses) of neurons-both of which
are embedded in the wall of the digestive tract
and extend from esophagus to anus

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The Enteric Nervous System 2 networks (or
plexuses) The myenteric plexus is located
between the longitudinal and circular layers of
muscle in the tunica muscularis and,
appropriately, exerts control primarily over
digestive tract motility. The submucous
plexus, as its name implies, is buried in the
submucosa. Its principal role is in sensing the
environment within the lumen, regulating GI blood
flow and controlling epithelial cell function. In
regions where these functions are minimal, such
as the esophagus, the submucous plexus is sparse
and may actually be missing

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GI Nerves
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The image shows part of the myenteric plexus in a
section of cat duodenum. The yellow circles
outline several enteric neurons.
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The Enteric Nervous System Within enteric
plexuses are 3 types of neurons, most of which
are multipolar Sensory neurons receive
information from sensory receptors in the mucosa
and muscle. At least 5 different sensory
receptors have been identified in the mucosa,
which respond to mechanical, thermal, osmotic and
chemical stimuli. Chemoreceptors sensitive to
acid, glucose and amino acids have been
demonstrated which, in essence, allows "tasting"
of lumenal contents. Sensory receptors in muscle
respond to stretch and tension.

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The Enteric Nervous System Within enteric
plexuses are 3 types of neurons, most of which
are multipolar Motor neurons within the enteric
plexuses control GI motility and secretion, and
possibly absorption. In performing these
functions, motor neurons act directly on a large
number of effector cells, including smooth
muscle, secretory cells (chief, parietal, mucous,
enterocytes, pancreatic exocrine cells) and GI
endocrine cells.Interneurons are largely
responsible for integrating information from
sensory neurons and providing it to
("programming") enteric motor neurons.

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The Enteric Nervous System Enteric neurons
secrete an intimidating array of
neurotransmitters (NTs). One major NT produced
by enteric neurons is acetylcholine. In general,
neurons that secrete acetylcholine are
excitatory, stimulating smooth muscle
contraction, increases in intestinal secretions,
release of enteric hormones and dilation of blood
vessels.

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The Enteric Nervous System Norepinephrine (NE)
is also used extensively for neurotransmission in
the GI tract, but it derives from extrinsic
sympathetic neurons the effect of NE is almost
always inhibitory and opposite that of
acetylcholine.

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The Enteric Nervous System The enteric nervous
system can and does function autonomously, but
normal digestive function requires communication
links between this intrinsic system and the
central nervous system. These links take the
form of parasympathetic and sympathetic fibers
that connect either the central and enteric
nervous systems or connect the CNS directly with
the digestive tract. Through these cross
connections, the gut can provide sensory
information to the CNS, and the CNS can affect
gastrointestinal function. Connection to the CNS
also means that signals from outside of the
digestive system can be relayed to the digestive
system for instance, the sight of appealing food
stimulates secretion in the stomach.

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The Enteric Nervous System In general,
sympathetic stimulation causes inhibition of GI
secretion and motor activity, and contraction of
gastrointestinal sphincters and blood vessels.
Conversely, parasympathetic stimuli typically
stimulate these digestive activities. Some of
the prominent communiques enabled by nervous
interconnections within the digestive tract have
been named as reflexes and serve to illustrate a
robust system of control. Examples include the
gastrocolic reflex, where distention of the
stomach stimulates evacuation of the colon, and
the enterogastric reflex, in which distention and
irritation of the small intestine results in
suppression of secretion and motor activity in
the stomach.

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The Enteric Endocrine System The second of the
two systems that control digestive function is
the endocrine system, which regulates function by
secreting hormones. Digestive function is
affected by hormones produced in many endocrine
glands, but the most profound control is exerted
by hormones produced within the GI tract. The
GI tract is the largest endocrine organ in the
body and the endocrine cells within it are
referred to collectively as the enteric endocrine
system. The best studied hormones are gastrin,
CCK, and secretin

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The Parietal Cell Mechanism of Acid Secretion
The best-known component of gastric juice is
HCl, the secretory product of the parietal, or
oxyntic cell. It is known that the capacity of
the stomach to secrete HCl is almost linearly
related to parietal cell numbers. When
stimulated, parietal cells secrete HCl at a
concentration of roughly 160 mM (equivalent to a
pH of 0.8). The acid is secreted into large
cannaliculi, deep invaginations of the plasma
membrane which are continuous with the lumen of
the stomach.

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Mechanism of Acid Secretion The H concentration
in parietal cell secretions is roughly 3 million
fold higher than in blood, and chloride is
secreted against both a concentration and
electric gradient. Thus, the ability of the
partietal cell to secrete acid is dependent on
active transport. The key player in acid
secretion is a H/K ATPase or "proton pump"
located in the cannalicular membrane. This
ATPase is magnesium-dependent, and not
inhibitable by ouabain.

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Mechanism of Acid Secretion The current model for
explaining acid secretion is as follows H are
generated within the parietal cell from
dissociation of water. The hydroxyl ions formed
in this process rapidly combine with carbon
dioxide to form bicarbonate ion, a reaction
cataylzed by CARBONIC ANHYDRASE Bicarbonate is
transported out of the basolateral membrane in
exchange for chloride. The outflow of bicarbonate
into blood results in a slight elevation of blood
pH known as the "alkaline tide". This process
serves to maintain intracellular pH in the
parietal cell.Chloride and potassium ions are
transported into the lumen of the cannaliculus by
conductance channels, and such is necessary for
secretion of acid.

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Mechanism of Acid Secretion The current model for
explaining acid secretion is as follows
Hydrogen ion is pumped out of the cell, into the
lumen, in exchange for potassium through the
action of the proton pump potassium is thus
effectively recycled. Accumulation of
osmotically-active hydrogen ion in the
cannaliculus generates an osmotic gradient across
the membrane that results in outward diffusion of
water - the resulting gastric juice is 155 mM HCl
and 15 mM KCl with a small amount of NaCl.

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Control of Acid Secretion Parietal cells bear
receptors for three stimulators of acid
secretion, reflecting a triumverate of neural,
paracrine and endocrine control Acetylcholine
(muscarinic type receptor) Gastrin Histamine
(H2 type receptor)

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The Enteric Endocrine System In contrast to
endocrine glands like the anterior pituitary
gland, in which essentially all cells produce
hormones, the enteric endocrine system is
diffuse single hormone-secreting cells are
scattered among other types of epithelial cells
in the mucosa of the stomach and SI. For
example, most of the epithelial cells in the
stomach are dedicated to secreting mucus, HCl or
a proenzyme called pepsinogen into the lumen of
the stomach. Scattered among these secretory
epithelial cells are G cells, which are endocrine
cells that synthesize and secrete the hormone
gastrin.

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The Enteric Endocrine System. Being a hormone,
gastrin is secreted into blood, not into the
lumen of the stomach. Similarly, other hormones
produced by the enteric endocrine system are
synthesized and secreted by cells within the
epithelium of the small intestine.

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The Enteric Endocrine System Like all endocrine
cells, cells in enteric endocrine system do not
simply secrete their hormone continuously, which
would not be very useful as a control system.
Rather, they secrete hormones in response to
fairly specific stimuli and stop secreting their
hormone when those stimuli are no longer present.
What stimulates the endocrinocytes in the
enteric endocrine system? As you might deduce, in
most cases these endocrine cells respond to
changes in the environment within the lumen of
the digestive tube. Because these cells are part
of the epithelium, their apical border is in
contact with the contents of the lumen, which
allows them to continually "taste" or sample the
lumenal environment and respond appropriately.

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INHIBITORY CONTROL acid at less than pH 2 is a
direct inhibitor of acid release acid in
duodenum releases secretin which inhibits gastric
secretion fatty acids, peptides stimulate
release of GIP (gastric inhibitory polypeptide)
and CCK (cholecystokinin)

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Hormones of the Gut Over 2 dozen hormones have
been identified in various parts of GI All of
them are peptides. Many of them are also found
in other tissues, especially the brain. Many act
in a paracrine manner as well as being carried in
the blood as true hormones. Their importance to
health is uncertain as few known deficiency
disorders have been found for any of
them. Gastrin, secretin, CCK, gherelin, SS, NPY,
PYY3-36

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Hormones of the Gut Gastrin is a mixture of
several peptides- most active -14 aa. It is
secreted by cells in the stomach and duodenum It
stimulates the exocrine cells of the stomach to
secrete gastric juice -a mixture of HCl and the
proteolytic enzyme pepsin. Secretin-27 aa It is
secreted by cells in the duodenum when they are
exposed to the acidic contents of the emptying
stomach. It stimulates the exocrine portion of
the pancreas to secrete bicarbonate into the
pancreatic fluid (thus neutralizing the acidity
of the intestinal contents).

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Hormones of the Gut Cholecystokinin (CCK)-A
mixture of peptides, of which an octapeptide (8
amino acids) is the most active. It is secreted
by cells in the duodenum and jejunum when they
are exposed to food. Acts on on the gall bladder
stimulating it to contract and force its contents
of bile into the intestine on the pancreas
stimulating the release of pancreatic digestive
enzymes into the pancreatic fluid. CCK also acts
on vagal neurons leading back to the medulla
oblongata which give a satiety signal (i.e.,
"that's enough food for now").

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Hormones of the Gut Somatostatin This mixture of
peptides acts on the stomach where it inhibits
the release of gastrin the duodenum where it
inhibits the release of secretin and
cholecystokinin the pancreas where it inhibits
the release of glucagon. Taken together, all of
these actions lead to a reduction in the rate at
which nutrients are absorbed from the contents of
the intestine. Somatostatin is also secreted by
the hypothalamus and the pancreas

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Hormones of the Gut PYY3-36 Peptide YY3-36
contains 34 amino acids, many of them in the same
positions as those in neuropeptide Y. But the
action of PYY3-36 is just the reverse of that of
NPY, being a potent feeding inhibitor. It is
released by cells in the intestine after meals.
The amount secreted increases with the number of
calories that were ingested.

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Hormones of the Gut PYY3-36 acts on the
hypothalamus to suppress appetite the pancreas
to increase its exocrine secretion of digestive
juices the gall bladder to stimulate the
release of bile. The appetite suppression
mediated by PYY3-36 works more slowly than that
of CCK and more rapidly than that of leptin. In
a recent human study, volunteers given PYY3-36
were less hungry and ate less food over the next
12 hours than those who received saline (neither
group knew what they were getting).

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Hormones of the Gut Ghrelin-28 aa is secreted
by endocrine cells in the stomach, especially
when one is hungry acts on the hypothalamus to
stimulate feeding This action counteracts the
inhibition of feeding by leptin and PYY3-36 .

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Now to the pancreas
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Hormones of the Pancreas Endocrine Pancreas
and EXOCRINE The pancreas houses two distinctly
different tissues. The bulk of its mass is
exocrine tissue and associated ducts, which
produce an alkaline fluid loaded with digestive
enzymes which is delivered to the SI to digest
foodstuffs. Scattered throughout the exocrine
tissue are several hundred thousand clusters of
endocrine cells which produce the hormones
insulin and glucagon, plus a few other hormones.

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Gross and Microscopic Anatomy of the Pancreas The
pancreas is a elongated organ, light tan or
pinkish in color, that lies in close proximity to
the duodenum. It is covered with a very thin
connective tissue capsule which extends inward as
septa, partitioning the gland into lobules. The
image below shows a canine pancreas in relation
to the stomach and duodenum.

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Pancreatic exocrine cells are arranged in
grape-like clusters called acini. The exocrine
cells themselves are packed with membrane-bound
secretory granules which contain digestive
enzymes that are exocytosed into the lumen of the
acinus. From there these secretions flow into
larger and larger, intralobular ducts, which
eventually coalesce into the main pancreatic duct
which drains directly into the duodenum.

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The pancreas is surrounded by a very thin
connective tissue capsule that invaginates into
the gland to form septae, which serve as
scaffolding for large blood vessels. Further,
these septae divide the pancreas into distinctive
lobules, as can clearly be seen in the image of
mouse pancreas below

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The Acinus exocrine pancreas is classified as a
compound tubuloacinous gland. -cells that
synthesize and secrete digestive enzymes are
arranged in grape-like clusters called acini In
standard histologic sections it is difficult to
discern their characteristic shape. In the image
of equine pancreas below, one fairly-good cross
section through an acinus is circled note the
wedge-shaped cells arranged around a small lumen


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Pancreatic Ducts Digestive enzymes from acinar
cells ultimately are delivered into the duodenum.
Secretions from acini flow out of the pancreas
through a tree-like series of ducts. Duct cells
secrete a watery, bicarbonate-rich fluid which
flush the enzymes through the ducts and play a
pivotal role in neutralizing acid within the
small intestine. Pancreatic ducts are classified
into 4 types

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Pancreatic ducts are classified into 4 types
Intercalated ducts- receive secretions from
acini. Intralobular ducts - are seen within
lobules and receive secretions from intercalated
ducts. Interlobular ducts are found between
lobules - vary considerably in size - transmit
secretions from intralobular ducts to the major
pancreatic duct. main pancreatic duct receives
secretion from interlobular ducts and penetrates
through the wall of the duodenum. In some
species, including man, the pancreatic duct joins
the bile duct prior to entering the intestine.

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Histology of panreatic ducts

Complex histology
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A low magnification image of equine pancreas (HE
stain) showing a large interlobular duct in
association with a pancreatic artery (A) and vein
(V). An intralobular duct (D) is seen on the
right side.

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Control of Pancreatic Exocrine Secretion As you
might expect, secretion from the exocrine
pancreas is regulated by both neural and
endocrine controls. During interdigestive
periods, very little secretion takes place, but
as food enters the stomach and, a little later,
chyme flows into the SI, pancreatic secretion is
strongly stimulated. Like the stomach, the
pancreas is innervated by the vagus nerve, which
applies a low level stimulus to secretion in
response to anticipation of a meal. However, the
most important stimuli for pancreatic secretion
comes from three hormones secreted by the enteric
endocrine system

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Cholecystokinin made and secreted by enteric
endocrine cells located in the duodenum. Its
secretion is strongly stimulated by the presence
of partially digested proteins and fats in the
SI. As chyme floods into the SI, CCK is released
into blood and binds to receptors on pancreatic
acinar cells, ordering them to secrete large
quantities of digestive enzymes.

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Secretin also a product of endocrinocytes
located in the epithelium of the proximal small
intestine. secreted in response to acid in the
duodenum, which of course occurs when acid-laden
chyme from the stomach flows through the pylorus.
The predominant effect of secretin on the
pancreas is to stimulate duct cells to secrete
water and bicarbonate. As soon as this occurs,
the enyzmes secreted by the acinar cells are
flushed out of the pancreas, through the
pancreatic duct into the duodenum.

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Gastrin very similar to CCK, is secreted in
large amounts by the stomach in response to
gastric distention and irritation. In addition to
stimulating acid secretion by the parietal cell,
gastrin stimulates pancreatic acinar cells to
secrete digestive enzymes. Stop and think about
this for a minute - control of pancreatic
secretion makes perfect sense. Pancreatic
secretions contain enzymes which are needed to
digest proteins, starch and triglyceride. When
these substances enter stomach, and especially
the SI, they stimulate release of gastrin and
CCK, which in turn stimulate secretion of the
enzymes of destruction.

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Pancreatic secretions are also the major
mechanism for neutralizing gastric acid in the
small intestine. When acid enters the small gut,
it stimulates secretin to be released, and the
effect of this hormone is to stimulate secretion
of lots of bicarbonate. As proteins and fats are
digested and absorbed, and acid is neutralized,
the stimuli for CCK and secretin secretion
disappear and pancreatic secretion falls off.

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Exocrine Secretions of the Pancreas Pancreatic
juice is composed of 2 secretory products
critical to proper digestion digestive enzymes
and bicarbonate. The enzymes are synthesized
and secreted from the exocrine acinar cells,
whereas bicarbonate is secreted from the
epithelial cells lining small pancreatic ducts.
Digestive Enzymes The pancreas secretes a
magnificent battery of enzymes that collectively
have the capacity to reduce virtually all
digestible macromolecules into forms that are
capable of, or nearly capable of being absorbed.
Three major groups of enzymes are critical to
efficient digestion

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PROTEASES Digestion of proteins is initiated by
pepsin in the stomach, but the bulk of protein
digestion is due to the pancreatic proteases.
Several proteases are synthesized in the
pancreas and secreted into the lumen of the SI.
The two major pancreatic proteases are trypsin
and chymotrypsin, which are synthesized and
packaged into secretory vesicles as an the
inactive proenzymes trypsinogen and
chymotrypsinogen.

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PROTEASES As you might anticipate, proteases
are rather dangerous enzymes to have in cells,
and packaging of an inactive precursor is a way
for the cells to safely handle these enzymes.
The secretory vesicles also contain a trypsin
inhibitor which serves as an additional safeguard
should some of the trypsinogen be activated to
trypsin following exocytosis this inhibitor is
diluted out and becomes ineffective - the pin is
out of the grenade.

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proteases Once trypsinogen and chymotrypsinogen
are released into the lumen of the SI, they must
be converted into their active forms in order to
digest proteins. Trypsinogen is activated by the
enzyme enterokinase, which is embedded in the
intestinal mucosa. Once trypsin is formed it
activates chymotrypsinogen, as well as additional
molecules of trypsinogen. The net result is a
rather explosive appearance of active protease
once the pancreatic secretions reach the SI.

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proteases Trypsin and chymotrypsin digest
proteins into peptides and peptides into smaller
peptides, but they cannot digest proteins and
peptides to single amino acids. Some of the
other proteases from the pancreas, for instance
carboxypeptidase, have that ability, but the
final digestion of peptides into amino acids is
largely the effect of peptidases in SI epithelial
cells.

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Pancreatic Lipase major form of dietary fat is
triglyceride, or neutral lipid. A triglyceride
molecule cannot be directly absorbed across the
intestinal mucosa. Must first be digested into a
2-monoglyceride and 2 free fatty acids. The
enzyme that performs this hydrolysis is
pancreatic lipase, which is delivered into the
lumen of the gut as a constituent of pancreatic
juice. Sufficient quantities of bile salts must
also be present in the lumen of the intestine in
order for lipase to efficiently digest dietary
triglyceride and for the resulting fatty acids
and monoglyceride to be absorbed. This means that
normal digestion and absorption of dietary fat is
critically dependent on secretions from both the
pancreas and liver.

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Pancreatic Lipase Pancreatic lipase has
recently been in the limelight as a target for
management of obesity. The drug orlistat
(Xenical) is a pancreatic lipase inhibitor that
interferes with digestion of triglyceride and
thereby reduces absorption of dietary fat.
Clinical trials support the contention that
inhibiting lipase can lead to significant
reductions in body weight in some patients.

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SIDE EFFECTS The most common side effects of
orlistat are oily spotting on underwear,
flatulence, urgent bowel movements, fatty or oily
stools, increased number of bowel movements,
abdominal pain or discomfort, and inability to
hold back stool (incontinence).
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From their web site The active ingredient in
alli attaches to some of the natural enzymes in
the digestive system, preventing them from
breaking down about a quarter of the fat you eat.
Undigested fat cannot be absorbed and passes
through the body naturally. The excess fat is not
harmful. In fact, you may recognize it in the
toilet as something that looks like the oil on
top of a pizza.
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Amylase The major dietary carbohydrate for many
species is starch, a storage form of glucose in
plants. Amylase is the enzyme that hydrolyses
starch to maltose (a glucose-glucose
disaccharide), as well as the trisaccharide
maltotriose and small branchpoints fragments
called limit dextrins. The major source of
amylase in all species is pancreatic secretions,
although amylase is also present in saliva of
some animals, including humans.

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Other Pancreatic Enzymes In addition to the
proteases, lipase and amylase, the pancreas
produces a host of other digestive enzymes,
including ribonuclease, deoxyribonuclease,
gelatinase and elastase.

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Bicarbonate and Water Epithelial cells in
pancreatic ducts are the source of the
bicarbonate and water secreted by the pancreas.
The mechanism underlying bicarbonate secretion
is essentially the same as for acid secretion
from parietal cells and is dependent on the
enzyme carbonic anhydrase. In pancreatic duct
cells, the bicarbonate is secreted into the lumen
of the duct and hence into pancreatic juice.