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Objectives
 After this lecture you will be able to:
 Review Intrinsic and extrinsic control of the different gut
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functions
Describe the GIT endocrine cells
Summarize the four routes by which regulatory substances in the
gut reach their target organs
Differentiate between gastrointestinal hormones, paracrines
regulatory peptides, and neurocrine substances and give
examples
List the major regulatory hormones and their major functions
Describe the major stimulus for secretion of each of the major
GIT hormone
Explain how incretins (GIP and GLPI) help in regulating blood
sugar levels
List the major regulatory peptides and their function
Intrinsic and extrinsic control of the
different gut functions
Endocrine cells of the gastric gland
GIT endocrine cells
 Columnar cells distributed throughout the gut epithelium, secrete
regulatory peptides and hormones
 Narrow apex and broad base (has secretary granules)
 Hormones and other regulatory peptide.
 Endocrine (hormones) released into the blood
 Substances (diffuse through extracellular matrix, paracrine substances)
Four routes by which regulatory substances in the gut
reach their target organs
Prostaglandins,
thromboxane etc.
Gastrointestinal hormones , paracrines
and neurocrine substances
 Endocrine hormones
 Carried by the blood
 Gastrin, Cholecystokinin (CCK), secretin, GIP,
motilin, somatostatin
 Paracrine (regulatory peptides)
 Released from endocrine cells in the GI mucosa
 Diffuse a short distance and act on target cells within
the GIT ( e.g, histamine).
 Neurocrine substances
 Released by neurons (substance P, VIP).
Gastrointestinal Hormones:
Gastrin
 Gastrin is secreted by the G-cells of gastric pylorus
and antrum, and duodenum
 Secretion is simulated by ACh, proteins, high pH and
distention of the duodenum.
 Functions:
 Major: Gastrin works together with acetylcholine and
histamine to stimulate acid secretion (H+) by parietal cells.
It binds to CCK2 receptor, a G-protein-coupled receptor
 Stimulates histamine secretion by enterochromaffin-like
cells (ECL)
 Stimulates chief cells to produce pepsinogen
 trophic effect means stimulate the growth of mucosa of
stomach , SI and LI
Parietal cells and acid secretion
Gastrointestinal Hormones
 Cholecystokinin-CCK
 Secreted mainly by duodenum
 Secretion is stimulated by Fatty acids,
mono glycerides, and amino acids in small
intestines.
 Major functions mediated through G-protein-coupled
receptor CCK1:
 Increases pancreatic enzyme secretion
 Contraction of gallbladder and relaxation of sphincter
of oddi
 Inhibition of gastric emptying and food intake
 augments the action of secretin
 trophic effect on pancreas
Gastrointestinal Hormones:
Secretin
 Secreted S-cells of duodenum
 Secretion is stimulated by Increased H+ concentration
(acidity of the chyme) in the duodenum, bile acids, fats,
and proteins.
 Major function
 Stimulation of pancreatic bicarbonate secretion
 augments the action of CCK
 Other functions
 Inhibits gastric acid secretion, increases gastric mucus
and pepsinogen
CCK and secretin
Incretins: GIP and GLP-1
 Incretins:
 Glucose-dependent-insulinotropic peptide (GIP)
used to be called Gastric Inhibitory peptide
 Glucagon-like peptide-1 (GLP-1)
 Secreted by the K cells duodenum and upper
jejunum in response to presence of glucose, amino
acids and fats in the lumen
 Major functions of GIP:
 Decreases gastric emptying (this is why it is called
entergostrone)
 Stimulates insulin secretion (β-cells) and Inhibits
glucagon (α-cells) release by pancreas
Gastrointestinal hormones: Incretins
(Glucagon-like peptide-1: GLP-1)
• Oral drugs that inhibit
Dipeptidyl peptidase-4
(DPP4) are useful for
treatment of type 2 or
maturity onset diabetes
• Type 2 diabetes is often
associated with obesity
Motilin
 Hormone Secreted by the M cells of the
duodenum and proximal part of jejunum
Secretion is stimulsated by presenbce of fsatys
and acid in the dpdenum
oRegulates motility of the gut between meals
oStimulates gastric emptying between meals
oStimulates duodenal motility
 Regulates tone of the lower esophageal sphincter
Somatostatin ( endocrine or paracrine)
 A hormone secreted by mucosa of the stomach
and intestinal cells, and delta cells of the
pancreas
 Inhibits the following activities
Gastric acid secretion by parietal cells
 Pepsinogen secretion by chief cells
 Release of hormones from the GIT
 Intestinal motility
 Contraction of gallbladder, which is
stimulated by CCK
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Paracrine substances
 Histamine
 Secreted by Enterochromaffin-like (ECL) in the
stomach
 Gastrin is the key stimulus for histamine secretion
 Major function: Acts on the H2 receptors of
parietal cells to stmulate HCl secretion.
 Increases gastric acid production by working
synergistically with gastrin and Ach (vagal,
parasympathetic stimulation)
 Blocking H2 receptors reduces acid secretion
 Histamine stimulates chief cells of the stomach to
secrete pepsinogen
Neurocrine:
 Released from enteric neurons of the GIT tract
 Substance P
 Major function: Contraction of intestinal smooth muscle
 Vasoactive Intestinal Peptide (VIP):
 Nitric Oxide (NO ) from smooth muscle stimulates its
release
 Major function: Produces relaxation of GI smooth muscles
in front of the peristaltic wave.
 It causes relaxation of sphincters.
Extrinsic hormonal control: Aldosterone
 Mineralocorticoid secreted by the adrenal cortex
 Stimulation: ACTH, low sodium intake, high potassium
levels,
 Main function: absorption of sodium and secretion of
potassium in the urine
 In the gut and salivary glands
 Absorption of sodium and the secretion of potassium