Classify GIT hormones List the source and functions of different GI hormones Explain the mechanism of action and regulation of secretion of different GI Hormones Describe the role of GI hormones in regulation of GI functions Explain the dysfunctions produced by alteration in secretion of GIT hormones

1. Gastrointestinal Hormones
Pandian M
Dept of Physiology
DYPMCKOP

2. Describe the source of GIT hormones, their
regulation and functions
1. Classify GIT hormones
1. List the source and functions of different GI hormones
1. Explain the mechanism of action and regulation of secretion of
different GI Hormones
1. Describe the role of GI hormones in regulation of GI functions
1. Explain the dysfunctions produced by alteration in secretion of
GIT hormones

3. Learning Objectives
The student will be able to: (MUST KNOW)
1. Classify GI hormones.
2. Name the source and functions of GI hormones.
3. Appreciate the role of GI hormones in the regulation of GI
functions.
4. Understand the dysfunctions produced by alteration in secretion of
GI hormones.

4. INTRODUCTION
• The hormones secreted from the endocrine cells of the GI tract are collectively known
as gastrointestinal hormones (GI hormones).
• Endocrine cells that secrete GI hormones are called enteroendocrine cells.
• Cells that secrete serotonin are called enterochromaffin cells, and cells that secrete
amines and polypeptides are called APUD cells (amine precursor uptake and
decarboxylation).
• APUD cells are also found in other organs like lungs. They are also called
neuroendocrine cells. Carcinoid tumors originate from these neuroendocrine cells.

5. TYPES OF GI HORMONES:
1. Gastrin family that includes cholecystokinin and
gastrin.
2. Secretin family that includes GIP, glucagon, secretin,
and VIP.
3. Other polypeptides.

6. GI HORMONES OF GASTRIN FAMILY
Gastrin
Source
• Gastrin is produced by G cells in the stomach that are located mainly in
the antral region.
• G cells are conical cells with apex projecting towards the lumen. Apical
surface of G cells contains numerous microvilli.
• Microvilli of G cells contain receptors for chemicals that mediate gastrin
release.
• Gastrin producing cells are also present in hypothalamus, anterior
pituitary, medulla and fetal pancreas.
• Gastrin as a neurotransmitter is also secreted from vagus and sciatic
nerve.

7. Structure
• Gastrin is a polypeptide hormone.
• Gastrin exhibits both macroheterogeneity and microheterogeneity.
TYPES OF GASTRIN: Depending on the number of amino acids they
possess, they are named as G 34, G 17 and G 14.
• Other types of gastrins are C-tetrapeptide (carboxyl terminal tetrapeptide,
which is also called minigastrin), and gastrin containing 45 amino acids
(megagastrin).
• However, G 17 is the principal gastrin secreted from the stomach and is
the major stimulator of gastric acid secretion.
• Though C-tetrapeptide executes all the actions of G-17, it has only 10% of
its physiological strength.

8. Metabolism
• Gastrin secreted from G cells enters general circulation. In blood, half-life of gastrin is less. Half-life of G
14 and G 17 is 2–5 min and of G 34 is about 15 min. Gastrin is inactivated in the intestine and degraded in
the kidney.
Functions
1. Stimulation of gastric acid and pepsin secretion.
2. Gastrin stimulates growth of gastric mucosa and mucosa of intestine. This is called trophic action of
gastrin.
3. It stimulates gastric motility.
4. It causes contraction of muscles at the gastro-esophageal junction
5. It stimulates exocrine pancreatic secretion.
6. It also stimulates insulin secretion.
7. It stimulates mass movement of large intestine.
8. It causes colonic contraction that initiates gastrocolic reflex after a meal. Therefore, usually defecation is
activated after a meal.
9. It stimulates histamine secretion from ECL (enterochromaffin like cells) in GI mucosa.

9. Mechanism of Action
• Gastrin acting on gastrin or CCK receptors on parietal cells increases
intracellular calcium concentration via second messenger, IP3.
• Increased cytosolic calcium activates protein kinase that stimulates H+–K+
ATPase to promote acid secretion.
Control of Gastrin Secretion
1. Stimuli that increase gastrin secretion: Gastric distention, products of
protein digestion in the stomach, increased vagal discharge via GRP (non-
cholinergic), epinephrine and calcium.
Hypergastrinemia occurs in Zollinger-Ellison syndrome. Gastrin secretion is
also elevated in pernicious anemia, in which acid secretion in the stomach is
less as parietal cells are damaged. This causes feedback release of gastrin from
G cells.

11. 2. Stimuli that decrease gastrin release: Acid in the stomach,
somatostatin, secretin, GIP, VIP, calcitonin and glucagon. Acid in the
antrum inhibits gastric secretion by negative feedback mechanism, which
is partly by direct action of acid on G cells and partly by release of
somatostatin.

13. Cholecystokinin
Source
• Secreted from I cells in the mucosa of upper small intestine. CCK is present as
neurotransmitter in cerebral cortex, in somatic nerves and in nerves of distal ileum and
colon.
Structure
• Cholecystokinin (CCK) is a polypeptide hormone.
• There are different forms of CCK depending on the number of amino acids present,
like CCK 58, CCK 39, CCK 33, CCK 12, CCK 8, and CCK 4 (carboxyl terminal
tetrapeptide).
• CCK secreted from duodenum and jejunum are usually CCK 12 and CCK 8. CCK in
the enteric and pancreatic nerves is mainly CCK 4. The forms of CCK in brain are
primarily CCK 58 and 8.
• Half-life of CCK is about 5 minutes.

14. Functions
1. CCK causes contraction of gall bladder and increases bile release.
2. It stimulates pancreatic secretion rich in enzymes. Therefore, CCK
is also called cholecystokinin-pancreozymin (CCK-PZ).
3. It also augments the action of secretin to produce alkaline pancreatic
secretion.
4. It inhibits gastric acid secretion.
5. It inhibits gastric motility, thereby delays gastric emptying.
6. Causes relaxation of sphincter of Oddi that allows both bile and
pancreatic juice to enter duodenum.
7. Stimulates growth of pancreas.

15. 8. Increases secretion of enterokinase.
9. Enhances motility of small intestine.
10. Stimulates colonic movements. This action mediates
gastrocolic reflex.
11. Augments contraction of pyloric sphincter. Therefore, prevents
reflux of duodenal contents into the stomach.
12. Stimulates glucagon secretion.
13. In brain, it acts as an anorexigenic neurotransmitter. It inhibits
food intake.
14. It also produces analgesia and anxiety.

16. Mechanism of Action
• There are two CCK receptors: CCK A and CCK B.
• CCK A receptors are mainly located in the peripheral structures like gall bladder,
pancreas, GI tract etc.
• CCK B receptors are present in central structures like brain areas.
• CCK acting on both receptors activates membrane phospholipase–C and stimulates
production of intracellular IP3 and DAG.
Regulation of Secretion
Factors that increase CCK secretion
1. Contact of intestinal mucosa with products of digestion especially fatty acids,
peptides and amino acids.
2. Bile and pancreatic juice: Bile and pancreatic juice facilitate digestion of protein
and fat. Therefore, they provide positive feedback for CCK secretion .

18. GI HORMONES OF SECRETIN FAMILY
Secretin
Source - S cells located in the mucosa of upper part of small intestine.
Structure - Polypeptide hormone containing 27 amino acids.
Functions
1. Secretin increases secretion of pancreatic juice rich in
bicarbonate (watery and alkaline pancreatic secretion).
2. It also increases alkaline bile secretion.
3. Augments the action of CCK to produce pancreatic secretion rich in
enzymes.
4. Decreases gastric acid secretion and motility.
5. Causes contraction of pyloric sphincter.

19. Mechanism of Action
• Secretin acts on adenylate cyclase on the cell membrane and increases
cytosolic formation of cAMP.
Regulation of Secretion
• Secretion of secretin is increased by acidic chyme and products of protein
digestion entering the upper part of intestine.
• Secretin stimulates watery and alkaline pancreatic secretion. When watery
and alkaline pancreatic juice enters intestine, the acidic content of upper
small intestine is neutralized.
• The increased pH of duodenal and upper jejunal content decreases secretin
secretion by feedback mechanism

21. GIP
Structure
• Glucose-dependent insulinotropic polypeptide (GIP) is a polypeptide
hormone containing 42 amino acids. This is also called gastric
inhibitory peptide (GIP).
Source
• GIP is produced by K cells present in the mucosa of duodenum and
jejunum.
Functions
1. It inhibits gastric secretion and motility.
2. It stimulates insulin secretion. For this function, GIP is considered
as an important physiological regulator of insulin secretion.

22. • Though other hormones like gastrin, CCK, secretin and glucagon also
stimulate insulin secretion, plasma insulin level of insulin in response to
GIP resembles the concentration of insulin attained following oral
glucose ingestion.
• Therefore, GIP is called glucose-like insulinotropic polypeptide.
• However, GLP-1, derived from glucagon appears to be more potent than
GIP in promoting insulin secretion.
• Hence, both GIP and GLP-1 are among the important physiological
regulator of insulin secretion from beta cells of pancreas.
Regulation of Secretion
• Secretion of GIP is increased by glucose and fat in the duodenum

23. VIP
Structure: Polypeptide containing 28 amino acids. It is formed from prepro-
VIP that contains both VIP and PHM-27, a closely related peptide.
Source
• VIP is secreted from mucosal cells of entire GIT, starting from stomach to
colon.
• It is found in the nerves of GIT, other autonomic nerves, blood and also in
brain.
• Its half-life is 2 minutes.
Functions
1. VIP markedly increases intestinal secretion rich in electrolytes and
water. Therefore, in excess it produces watery diarrhea.
2. It causes vasodilation. Therefore, it decreases blood pressure.

24. 3. It decreases GI motility. It causes relaxation of
intestinal smooth muscle including sphincters.
4. It potentiates the action of acetylcholine on salivary
glands.
5. It inhibits gastric acid secretion.
Clinical Significance
•The tumor of VIP secreting cells is called VIPoma.
Profuse watery diarrhea and hypotension are major
features of VIPoma.

25. Glucagon
• This is structurally similar with glucagon secreted from A (α) cells of
pancreas. In GIT, it is secreted from A cells in the stomach and L cells in
intestine, where it is known as enteroglucagon. This produces
hyperglycemia.
SOURCE: Glucagon is mainly produced from A (α) cells in pancreas and
L cells in intestine.
• A cells: In A cells, preproglucagon is processed to form glucagon and
major proglucagon fragments (MPGF).
• L cells: In L cells, it is processed to form glucagon, glicentin and
glucagon-like peptides (GLP).
• Both A and L cells also produce oxyntomodulin and glicentin related
polypeptide (GRPP)

26. Glucagon-Like Polypeptides: GLP 1 and GLP 2 and both are also
produced in brain.
• GLP 1 is a potent stimulator of insulin secretion.
• GLP 2 does not have definitive biological activity.
• However, GLP 2 produced in the brain inhibits food intake and acts as a
neurotransmitter in the neurons that project from NTS to dorsomedial
nucleus of hypothalamus.
Oxyntomodulin & GRPP
• Both A and L cells also produce oxyntomodulin and glicentin-related
polypeptide (GRPP).
• Oxyntomodulin inhibits gastric acid secretion.

27. OTHER GI HORMONES
Motilin
Structure & Source
• This is a polypeptide hormone containing 22 amino acids. It is secreted
from enterochromaffin cells and Mo cells present in the mucosa of all
parts of GIT, except esophagus and rectum. It acts on G-protein coupled
receptors on enteric neurons.
Functions
• It causes contraction of intestinal smooth muscle and therefore,
increases GI motility, especially in the interdigestive phase.
• It is a major regulator of migrating motor complex (MMC), that
regulates GI motility between meals.

28. • Secretion of motilin is decreased following ingestion of a meal
and its concentration remains low until the digestion and
absorption of that meal is complete. Then the concentration
increases and activates MMC that sweeps and cleans the intestine.
Thus, it prepares the intestine for next meal.
Applied Physiology
• Erythromycin can be used in patients having hypomotility of GI
tract, as this antibiotic and its derivative bind to motilin receptors
and facilitate intestinal motility.

29. Other Peptides
Neurotensin
• This is a polypeptide hormone containing 13 amino acids. It is produced
by neurons and mucosal cells of intestinal epithelium, mainly in ileum. It
inhibits GI motility but increases ileal blood flow.
GRP
• Gastrin releasing polypeptide (GRP) is a polypeptide containing 27 amino
acids.
• It is secreted from non-cholinergic vagal fibers.
• It mediates gastrin release via non-cholinergic vagal stimulation.
• The 10 amino acid residues at the carboxyl terminal of GRP is almost
similar to the bombesin of amphibians.

30. Somatostatin
• This is a polypeptide containing either 14 (SS 14) or 28 (SS 28) amino acids.
• Somatostatin is secreted from GIT, hypothalamus and D cells of pancreas.
• It inhibits gastrin secretion.
• It also inhibits secretion of VIP, GIP, secretin, and motilin.
• It is an inhibitory neurotransmitter in many parts of brain, especially in hypothalamus
and pituitary.
Guanylin
Structure and Source
• This is a polypeptide hormone containing 15 amino acids. It is secreted from the cells of
intestinal mucosa. In human, it is produced by Paneth cells (endocrine cells located in
the crypts of Lieberkuhn of small intestine).

31. Mechanism of Action
• It acts by stimulating the activity of guanylyl cyclase which increases the concentration of
cGMP. The cGMP in turn increases activity of chloride channels and increases chloride
secretion into the intestine.
Functions
• Guanylin increases secretion of chloride ions into the intestinal lumen and therefore
regulates fluid movement across intestinal tract.
• Guanylin receptors are present in kidney, liver and female reproductive tract.
• In these organs, guanylin appears to control fluid movement and particularly integrates the
actions of intestine and kidneys.
Applied Physiology
• Enterotoxins of some strains of E. coli that cause diarrhea have structural similarity with
guanylin. They activate guanylin receptors in intestine and produce fluid secretion into the
intestinal lumen.

32. TRH
• This is structurally similar to the hypothalamic TRH. But, as it does not enter
circulation, it does not produce any effect on thyroid. However, it is involved in the
regulation of secretory immunity of intestine.
ACTH
• Structurally, it is similar to the ACTH of anterior-pituitary. The function of
intestinal ACTH is not clearly known.
Ghrelin
• It is a 28 amino acid polypeptide secreted mainly from stomach. It has more
systemic effects than local actions.
• It is a strong orexigenic agent that increases food intake by acting on arcuate
nucleus of hypothalamus.
• It stimulates secretion of growth hormone from anterior pituitary.

33. Peptide YY
• It is a polypeptide hormone secreted from small intestine and colon.
• It inhibits gastric secretion and motility. Hence, it is proposed to be an effective
gastric inhibitory peptide.
• Its secretion is stimulated by presence of fat in jejunum.
• Though, structurally it resembles neuropeptide Y that stimulates food intake, peptide
YY inhibits feeding.
Substance P
• Substance P is secreted from endocrine cells and neurons of entire GIT starting from
stomach to colon. It increases intestinal motility

34. Referred :-
• Text book of Medical Physiology
• Guyton, 12th edition,
• Text book of Medical Physiology
• Indu khurana, & Sembulingam
• Fundamental Physiology
• L.P.Reddy
• Net source

35. THANK YOU . . .