This document discusses gastrointestinal hormones and their regulation of gastrointestinal function. It describes various hormones like gastrin, cholecystokinin, secretin, gastric inhibitory peptide, and somatostatin. It explains where these hormones are produced, their targets, and main actions. Different hormones regulate processes like gastric acid secretion, pancreatic enzyme secretion, gallbladder contraction, and gastrointestinal motility. The document also discusses the regulation of hormone secretion and different pathways of action like endocrine, paracrine, autocrine, neurocrine, and juxtacrine signaling.
Endocrine regulation : 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
Gastrointestinal Hormones by Pandian M, Dept of Physiology DYPMCKOP, for MBBS...Pandian M
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
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.
Endocrine regulation : 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
Gastrointestinal Hormones by Pandian M, Dept of Physiology DYPMCKOP, for MBBS...Pandian M
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
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.
LOCATION: WALL OF GUT
NEURONS: 100 MILLIONS
GIT MOVEMENTS AND SECRETIONS
COMPOSED: TWO PLEXUSES
OUTER PLEXUS (MYENTERIC AND AUERBACH'S PLEXUS)
INNER PLEXUS (MEISSNER'S PLEXUS AND SUBMUCOSAL PLEXUS)
MYENTERIC PLEXUS
GI MOVEMENTS
SUBMUCOSAL PLEXUS
SECRETION AND LOCAL BLOOD FLOW
LOCATION: WALL OF GUT
NEURONS: 100 MILLIONS
GIT MOVEMENTS AND SECRETIONS
COMPOSED: TWO PLEXUSES
OUTER PLEXUS (MYENTERIC AND AUERBACH'S PLEXUS)
INNER PLEXUS (MEISSNER'S PLEXUS AND SUBMUCOSAL PLEXUS)
MYENTERIC PLEXUS
GI MOVEMENTS
SUBMUCOSAL PLEXUS
SECRETION AND LOCAL BLOOD FLOW
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3. Regulation of GI function
Endocrine regulation : 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
MUHAMMAD RAMZAN UL REHMAN 3
4. Regulation of GI function
Autocrine : regulatory peptide secreted by the cells acting on themselves.
Juxtacrine : 1 regulatory peptide acts on many target cells.
Neurocrine : through nerves and neurotransmitters.
MUHAMMAD RAMZAN UL REHMAN 4
6. Enteroendocrine cell (EEC)
Hormone-secreting cells in the mucosa of stomach, small intestine, colon
produce by : G cell, S cell
Produce 5-HT & hormones : enterochromaffin cell
Produce amine or polypeptide : neuroendocrine cell (APUD: Amine Precursor Uptake and
Decarboxylase)
MUHAMMAD RAMZAN UL REHMAN 6
7. Enteroendocrine cell (EEC)
Have 2 types
Open-type : apical membrane contact with GI lumen (receptor), secretion occurs in basolateral
membrane ex. G cell
Closed-type : No contact with luminal surface ex. Enterochromaffin-like cell (ECL) which
secretes histamine
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8. GI hormones
Classified by similarity in structure and function
1. Gastrin family : gastrin, CCK
2. Secretin family : secretin, glucagon, glicentin, VIP, GIP
3. Others (not fit in either family) : motilin, substance P, GRP, guanylin
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9. Gastrin
Produced by G cell in the mucosal gland of gastric antrum and duodenum
Can be found in fetal pancreatic islet, hypothalamus, medulla oblongata, vagus n. (unidentified
function)
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10. Structure of gastrin
Polypeptide hormone with multiple forms
1. Macroheterogenity : diff in length of peptide chain
2. Microheterogenity : diff on derivatization of amino acid residues
ex. Sulfation of tyrosine (6th aa residue from C-terminal), amidation of the C-terminal
phynylalanine
MUHAMMAD RAMZAN UL REHMAN 10
11. Structure of gastrin
Preprogastrin (101 aa) is processed into 3 fragments
1. G34 : 34 aa secreted mainly by duodenal G cell
2. G17 : 17 aa secreted mainly by antral G cell
3. G14 : 14 aa
All forms have the same C-terminal configuration
MUHAMMAD RAMZAN UL REHMAN 11
13. Gastrin
Different forms, different activity, different tissues that are found
G17 : principal form of gastric acid secretion (more active and more amount than G34)
Half Life (t1/2) : G14, G17 2-3 min in blood.
G34 15 min
Inactivated in kidney, small bowel
MUHAMMAD RAMZAN UL REHMAN 13
14. Action of gastrin
Stimulation of gastric acid and pepsin secretion
Stimulation of mucosal growth in stomach, SB, colon (trophic action)
Stimulation of gastric motility
Release of histamine from ECL cell
Stimulate insulin secretion after protein meal (not CHO)
+/- constriction of LES
MUHAMMAD RAMZAN UL REHMAN 14
16. Regulation of gastrin secretion
↑ gastrin secretion
Luminal : peptide, aa (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
MUHAMMAD RAMZAN UL REHMAN 16
17. Feedback inhibition of gastrin
Acid in antrum inhibit gastrin secretion by 2 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.
MUHAMMAD RAMZAN UL REHMAN 17
18. Cholecystokinin-Pancreozymin
(CCK)
Also shows macro- and microheterogenity Prepro-CCK is processed into several fragments
CCK58, CCK39, CCK33, CCK22 ,CCK12, CCK8
Every forms has the same 5 aa at C-terminal as gastrin
Every forms has amidation of C-terminal, sulfation of 7thtyrosine from C-terminal
MUHAMMAD RAMZAN UL REHMAN 18
20. CCK
Secreted by I cell in duodenum and jejunum
Also found in nerves in distal ileum and colon, neurons in brain (regulation of food intake)
CCK8, CCK22, CCK33 : principal circulating forms secreted in response to meal
Enteric & pancreatic nerve : CCK4
Brain : CCK8, CCK58
MUHAMMAD RAMZAN UL REHMAN 20
21. Action of CCK
Gall bladder contraction, sphincter of Oddi relaxation
↑ pancreatic enzyme secretion
Augment effect of secretin in producing alkaline pancreatic juice
↓ gastric emptying
Trophic effect on pancrease
MUHAMMAD RAMZAN UL REHMAN 21
22. Action of CCK
↑ secretion of enterokinase
↑ motility of small intestine and colon
Augment contraction of pyloric sphincter (↓ duodenal reflux)
↑ glucagon secretion (work with gastrin)
Induced satiety by acting through hypothalamus
MUHAMMAD RAMZAN UL REHMAN 22
23. Mechanism of action
Through CCK receptor (2 type)
1. CCK-A : locates in periphery, brain
2. CCK-B : locates in brain
CCK bind to receptor activate phospholipase C → IP3, DAG → ↑ intracellular Ca → activate
protein kinase → release of granule (pancreatic enzyme)
MUHAMMAD RAMZAN UL REHMAN 23
24. Mechanism of action
CCK also stimulate vagus nerve to pancrease (via CCK-A receptor) → release of Ach, GRP, VIP →
fusion of granule with membrane and release of pancreatic enzyme
Gastrin receptor is very similar to CCK-B receptor.
MUHAMMAD RAMZAN UL REHMAN 24
26. Control of CCK secretion
Most potent stimulator of CCK release is lipid
Peptones, amino acid also increase CCK release but CHO has little effect.
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)
MUHAMMAD RAMZAN UL REHMAN 26
27. 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)
Match the release of CCK, pancreatic enzyme and the need for enzyme
to digest foods
These peptides are degraded by pancreatic trypsin (if there are
proteins in duodenum, these peptides won’t be degraded and CCK will
be released )
MUHAMMAD RAMZAN UL REHMAN 27
28. 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)
MUHAMMAD RAMZAN UL REHMAN 28
29. 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
MUHAMMAD RAMZAN UL REHMAN 29
30. Action of secretin
↑ pancreatic enzyme secretion (augment CCK)
↓ gastric acid secretion
Pyloric sphincter contraction
Stimulate growth of exocrine pancrease (work with CCK)
MUHAMMAD RAMZAN UL REHMAN 30
33. Effect of secretin on bile secretion
Produce a watery bile rich in HCO3
Activate via cAMP → stimulate CFTR (Chloride channel) and Cl– HCO3 exchanger
Work in concert with glucagon, VIP
MUHAMMAD RAMZAN UL REHMAN 33
36. 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
MUHAMMAD RAMZAN UL REHMAN 36
37. Gastric inhibitory peptide (GIP)
42 amino-acid polypeptide
Produced by K cell in duodenal and jejunal mucosa
Stimulated by glucose and fat in duodenum, acid in stomach
Inactivated by dipeptidyl-peptidase IV (DPP-IV)
in many tissues and in portal circulation
MUHAMMAD RAMZAN UL REHMAN 37
38. Action of GIP
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
Oral glucose can stimulate larger amount of insulin release than IV glucose
MUHAMMAD RAMZAN UL REHMAN 38
39. Enteric factors increasing insulin
release
CCK, GIP, GLP-1, Glucagon
GIP is also called glucose-dependent insulinotropic polypeptide by this action
GLP-1 is more potent than GIP (limited study)
GIP, GLP-1 act via protein kinase A pathway (increased cAMP and cytosolic calcium)
MUHAMMAD RAMZAN UL REHMAN 39
40. Glucagon-Like Peptide 1 (GLP-1)
30 amino-acid polypeptide
Incretin hormone : intestinal hormone secreted in response to nutrient ingestion which
potentiate glucose-induced insulin release
Produced by L cell in ileum and colon, pancreatic alpha cell, neurons in hypothalamus, pituitary
gland
2 bioactive forms : GLP-1[7-36] amide , GLP-1[7-37] both forms are equipotent, same t1/2
MUHAMMAD RAMZAN UL REHMAN 40
42. Glucagon
Produced by alpha cell of pancreatic islet
Action :
Increase glycogenolysis
Increase gluconeogenesis
hyperglycemia
MUHAMMAD RAMZAN UL REHMAN 42
43. Glicentin
69 amino-acid polypeptide derived from proglucagon
Secreted from L cell along with GLP-1 and GLP-2
Action : stimulation of insulin secretion, inhibit gastric acid secretion, regulation of gut motility,
stimulation of intestinal growth
MUHAMMAD RAMZAN UL REHMAN 43
44. Vasoactive intestinal peptide (VIP)
28 amino-acid polypeptide
Found in ENS neurons (both myenteric and submucosal plexus), brain, autonomic nerves
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
MUHAMMAD RAMZAN UL REHMAN 44
45. Action of VIP
↑ secretion of E’lyte and water from small bowel
Intestinal circular smooth ms relaxation
Longitudinal smooth muscle contraction
↑ pancreatic secretion
Inhibit gastric acid secretion and motility
Potentiate axn of Ach in salivary gland
VIPoma : presented with profused diarrhea
MUHAMMAD RAMZAN UL REHMAN 45
46. Motilin
22 amino-acid polypeptide
Secreted by enterochromaffin cell and M cell in duodenum, jejunum
Acts on G-protein coupled receptor on enteric neurons in stomach, duodenum → GI tract
smooth muscle contraction
Its circulating level increased at interval of 90-100 mins in the interdigestive state
MUHAMMAD RAMZAN UL REHMAN 46
47. Motilin
Major regulator of MMCs (Migrating Motor Complex) that move through the stomach and small
intestine every 90 mins in fasted person
Motilin secretion is inhibited after ingestion
Vagal nerve may play some role in motilin secretion
Erythromycin bind to motilin receptor → ↑ GI motility in constipated person
MUHAMMAD RAMZAN UL REHMAN 47
48. 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
MUHAMMAD RAMZAN UL REHMAN 48
49. somatostatin
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)
MUHAMMAD RAMZAN UL REHMAN 49
50. 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
MUHAMMAD RAMZAN UL REHMAN 50
52. Hormone Source Target Action
Cholecystokinin I cell in duo,
jeju, neurons in
ileum, colon
Pancrease
gallbladder
↑enz secretion
↑contraction
GIP K cell in duo,
jeuju
pancrease ↓fluid absorp
↑insulin release
Gastrin G cell in
antrum, duo
Parietal cell ↑acid secretion
↑motility
GRP Vagus nerve G cell Gastrin release
MUHAMMAD RAMZAN UL REHMAN 52
53. Hormone Source Target Action
Glucagon Alpha cell in
pancreatic islet
liver ↑glycogenolysis
↑gluconeogenesis
Guanylin Ileum, colon Small and large
intestine
↑fluid secretion
Motilin EC cell, Mo cell
in upper GI tract
Eso sphincter
Stomach, duo
Smooth muscle
contraction
Neurotensin Neurons, ECC in
ileum
Intestinal
smooth muscle
↓ GI motility
↑ blood flow
MUHAMMAD RAMZAN UL REHMAN 53
54. Hormone Source Target Action
Peptide YY L cell in ileum,
colon
Stomach
Pancrease
↓ vagal mediated acid
secretion
↓ enz and fluid
secretion
Secretin S cell in small
intestine
Pancrease
Stomach
↑HCO3 and fluid
secretion by
pancreatic ducts
↓ gastric a secretion
somatostatin D cell in stomach
, duodenum,
pancreatic islet
Stomach
Intestine
Pancrease
Liver
↓ gastrin release
↑fluid absorption
↑smm contraction
↓endo/exocrine
secretion
↓bile flow
MUHAMMAD RAMZAN UL REHMAN 54
55. Hormone Source Target Action
Substance P Enteric neurons Intestine
Pancrease
↑GI motility
↓HCO3 secretion
VIP ENS neurons Small intestine
Pancrease
smm contraction
↑SB secretion
↑pancreatic secretion
MUHAMMAD RAMZAN UL REHMAN 55
56. Thank You
BY MUHAMMAD RAMZAN UL REHMAN
MUHAMMAD RAMZAN UL REHMAN 56