The classical GI hormones are secreted by epithelial cells lining the lumen of the stomach and small intestine. These hormone-secreting cells - endocrinocytes - are interspersed among a much larger number of epithelial cells that secrete their products (acid, mucus, etc.) into the lumen or take up nutrients from the lumen. GI hormones are secreted into blood, and hence circulate systemically, where they affect function of other parts of the digestive tube, liver, pancreas, brain and a variety of other targets.

1. 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
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)

2. The gastrointestinal hormones (or gut hormones) constitute a group of hormones secreted by
enteroendocrine cells in the stomach, pancreas, and small intestine that control various
functions of the digestive organs.
Enteroendocrine cells do not form endocrine glands but are spread throughout the digestive
tract. They exert their autocrine and paracrine actions that integrate all of gastrointestinal
function.
GI Hormone
Regulation of GI function
 Endocrine regulation : Enteroendocrine cells (EEC) secretes regulatory peptide or hormones
that travel via blood stream to remote target organ. Ex. gastrin, secretin
 Paracrine regulation : Regulatory peptide secreted by EEC acts on a nearby target cell by
diffusion through interstitial space. Ex. histamine, 5-HT
Classification of GI hormones
The gastrointestinal hormones can be divided into the following groups based upon their
chemical structure.
Gastrin-cholecystokinin family: gastrin and cholecystokinin
Secretin family: secretin, glucagon, vasoactive intestinal peptide (VIP) and gastric inhibitory
peptide (GIP)
Somatostatin family
Motilin family
Substance P

3. GI Hormone Gastrin
 Gastrin is a peptide hormone that stimulates secretion of
gastric acid (HCl) by the parietal cells of the stomach and
aids in gastric motility.
 It is released by G cells in the antrum of the stomach,
duodenum, and the pancreas.
 It binds to cholecystokinin B receptors to stimulate the
release of histamines in enterochromaffin-like cells.
 It induces the insertion of K+/H+ ATPase pumps into the
apical membrane of parietal cells (which in turn increases
H+ release).
 Release is inhibited by highly acidic pH (< 2.0).
Regulation of gastrin secretion
 ↑ gastrin secretion
 Luminal : peptide, amino acids (Phy,
Tryp), gastric distention
 Neural : vagal stimulation via GRP (can’t
be blocked by atropine)
 Blood : Ca, epinephrine
↓ gastrin secretion
Luminal : acid, somatostatin
Blood : secretin, GIP, VIP, glucagon, calcitonin

4. Gastrin secretion and regulation
Feedback inhibition of gastrin
 Acid in antrum inhibit gastrin secretion by two ways
1. Direct action on G cell
2. Stimulate release of somatostatin by D cell
 In condition which parietal cells are damaged, pernicious anemia, gastrin level is
elevated.

5.  Gastrin is produced at excessive levels.
 Often by a gastrinoma (gastrin-producing tumor, mostly benign)
of the duodenum or the pancreas.
In autoimmune gastritis, the immune system attacks the
parietal cells leading to hypochlorhydria (low stomach
acidity).
This results in an elevated gastrin level in an attempt to
compensate for increased pH in the stomach
Eventually, all the parietal cells are lost and achlorhydria
results leading to a loss of negative feedback on gastrin
secretion.
How it occurs:
Zollinger-Ellison syndrome
Cholecystokinin-Pancreozymin (CCK)
 Cholecystokinin (CCK or CCK-PZ) is a peptide hormone of the gastrointestinal system
responsible for stimulating the digestion of fat and protein.
 Cholecystokinin (pancreozymin) is synthesized by I-cells in the mucosal epithelium of
the small intestine.
 Secreted in the duodenum, the first segment of the small intestine.
 Causes the release of digestive enzymes and bile from the pancreas and gallbladder.

6. CCK secretion
Cholecystokinin-Pancreozymin (CCK)
 CCK is composed of varying numbers of amino acids depending on post-translational modification
of the CCK gene product, preprocholecystokinin.
 CCK8, CCK22, CCK33 : principal circulating forms secreted in response to meal.
 Every forms has the same 5 aa at C-terminal as gastrin

7. Action of CCK
 Gall bladder contraction, sphincter of Oddi
relaxation
 ↑ pancreatic enzyme secretion
 Augment effect of secretin in producing
alkaline pancreatic juice
 ↓ gastric emptying
 Induced satiety by acting through
hypothalamus
Mechanism of action
 Through CCK receptor (2 type)
1. CCK-A : Primarily gastrointestinal tract, lesser
amounts in the CNS
2. CCK-B : Primarily CNS, lesser amounts in the
gastrointestinal tract
 CCK bind to receptor activate phospholipase
C → IP3, DAG → ↑ intracellular Ca → activate
protein kinase → release of granule
(pancreatic enzyme)

8. Mechanism of action Pancreatic cell type
Control of CCK secretion
Most potent stimulator of CCK release is lipid
Peptones, amino acid also increase CCK release.
Also secreted in response to CCK-releasing factor
Positive feedback : CCK → enzyme release → more digestive products → more CCK (stop when
digestive products move to next part)

9. CCK-releasing peptide & monitor peptide
 CCK-RP is secreted from duodenal mucosa, and
monitor peptide by pancreatic acinar cell
 Secreted in response to fat, protein digestive products,
and also to neural input (cephalic phase)
 These peptides are degraded by pancreatic trypsin (if
there are proteins in duodenum, these peptides won’t
be degraded and CCK will be released )
Secretin
 27 amino-acid polypeptide
 Secreted by S cell located deeply in the mucosal gland of duodenum and jejunum
 Similar structure with glucagon, VIP, GIP
 Only 1 form has been isolated
 t1/2 : 5 min
 Stored in an inactive form (prosecretin)
Action of secretin
 Most potent humoral stimulator of fluid and HCO3 secretion by pancrease
 Acts in concert with CCK, Ach to stimulate HCO3 secretion
 ↑ HCO3 secretion by duct cells of pancrease and biliary tract→ ↑secretion of a watery,
alkaline pancreatic juice
 Acting through cAMP

10.  ↑ pancreatic enzyme secretion (augment CCK)
 ↓ gastric acid secretion
 Pyloric sphincter contraction
 Stimulate growth of exocrine pancrease (work
with CCK)
Action of secretin
Mechanism of action

11. Action of secretin & CCK in pancrease Control of secretin secretion
 Secretin is secreted in response to
protein digestive products, bile acid,
fatty food and increased acidity in
duodenal content (pH< 4.5-5)
 Inhibited by somatostatin and Met-
enkephalin
 Secretin release may be mediated by
secretin-releasing peptide
Gastric inhibitory polypeptide (GIP)
 GIP is a member of the secretin family of hormones.
 It is derived from a 153-amino acid proprotein encoded by the GIP gene and circulates as
a biologically active 42-amino acid peptide.
 It is synthesized by K cells, which are found in the mucosa of the duodenum and the
jejunum of the gastrointestinal tract.
 Like all endocrine hormones, it is transported by blood.
 GIP receptors are seven-transmembrane proteins found on beta-cells in the pancreas.

12. Action of GIP
Stimulated by glucose and fat in duodenum, acid in stomach
Mild effect in decreasing gastric motility
Inhibit gastric acid secretion by directly inhibit parietal cells or indirectly inhibit gastrin
release from antral G cells (via somatostatin)
Stimulate insulin release from pancreatic islet in response to duodenal glucose and fatty acid
For this action, it has also been referred to as glucose-dependent
insulinotropic peptide.
Vasoactive intestinal peptide (VIP)
 28 amino-acid polypeptide
 Released in response to esophageal
and gastric distention, vagal
stimulation, fatty acid and ethanol in
duodenum
 Amino acid and glucose don’t affect
VIP release
 Half life 2 min in circulation
Action of VIP
 VIP seems to induce smooth muscle relaxation
(stomach, gallbladder), stimulate secretion of
water into pancreatic juice and bile, and cause
inhibition of gastric acid secretion and
absorption from the intestinal lumen.
 It also has the function of stimulating
pepsinogen secretion by chief cells.
 VIP a crucial component of the mammalian
circadian timekeeping machinery.
 It is also found in the heart and has significant
effects on the cardiovascular system. It causes
coronary vasodilation.

13. Somatostatin
 Growth hormone inhibitory hormone (GH-IH)
 First found in hypothalamus
 Secreted by D cell in stomach, duodenum,
pancreatic islet
 Secreted in larger amount into gastric lumen
> circulation
 Released in response to acid in stomach
Presented in 2 forms
1.Somatostatin 14 : prominent in hypothalamus
2.Somatostatin 28 : prominent in GI tract
Acts through G-protein couple receptor (inhibit
adenylate cyclase)
Somatostatin
Action of somatostatin
 Inhibit secretion of gastrin, VIP, GIP, secretin, motilin, GH, insulin, glucagon
 ↑ fluid absorption and ↓ secretion from intestine
 ↓ endocrine and exocrine pancreatic secretion
 ↓ bile flow and gall bladder contraction
 ↓ gastric acid secretion and motility
 ↓ absorption of glucose, amino acid, triglyceride