This document discusses several gastrointestinal hormones and their functions. It begins by noting there are over 30 peptides secreted in the digestive tract, making the gut the largest endocrine organ. These peptides act as regulatory hormones, neurotransmitters, and growth factors. The document then focuses on several key hormones: cholecystokinin stimulates gallbladder contraction and pancreatic enzyme secretion; gastrin stimulates acid and pepsin secretion; secretin stimulates pancreatic bicarbonate secretion; and glucagon-like peptide 1 potentiates glucose-dependent insulin secretion. Finally, it mentions somatostatin is the main inhibitory peptide and suppresses secretion of other hormones.

1. Gastrointestinal Hormone
and Disorders -I
Binaya Tamang
UCMS-TH

2. Introduction
• There are more than 30 peptides expressed within the digestive tract.
• Making the gut the largest endocrine organ in the body.
• Secreted by pancreatic islet cell ( somatostatin), GUT mucosa ( CCK)
and nerve of intestine ( VIP)
• They can act as
• Regulatory peptide hormone
• Peptide neurotransmitters
• Growth factors
• Collectively, they influence motility secretion digestion and absorption in
the GUT.
• Regulate bile flow and secretion of pancreatic hormones

3. Principal GUT regulatory protein: Two Family
üGastrin family
• Cholecystokinin
• Gastrin ( little-17aa and big-34aa)
üSecretin-Glucagon family
• Secretin
• vasoactive intestinal polypeptide (VIP)
• Glucose dependent insulinotropic polypeptide (GIP)
Lets describe some important types

4. Cholecystokinin (CCK):
• Linear peptide hormone (33aa).
• Preprocholecystokinin ( 115aa) by
cleavage àCCK
• Secreted by C or I cells of duodenum
and jejunum.
• Main stimulus: mix polypeptides with
aa ( Trp and Phe), gastric juice and FA
>9C
Fxn:
• stimulates gallbladder contraction
and bile flow
• To reach inside intestineà relaxes
sphincter of Oddi
• Increases secretion of digestive
enzymes from pancreas.
• Increases small intestine motility.
• Has a role as indicating satiety ( I am
not hungry anymore)

5. Gastrin
• Secreted by G cells of the stomach and proximal part of duodenum.
• Preprogastrin by cleavage (101 aa) à gastrin.
• Big gastrin (34 aa) and Small gastrin (17aa)
• Biologically active part is C terminal pentapeptide (5aa).
• In market, synthetic peptide called as Pentagastrin à used in gastric
function test.
• Stimulated by : meals, aa (Gly, Trp, Phe), alcohol, caffeine, smelling,
chewing, tasting (vagal stimulation).
• FXN: stimulates acid (HCL) and prorenin, pepsin secretion, also
stimulates pancreatic secretion, intrinsic factor.
• Excessive gastrin secretion: gastrin producing tumors as Zollinger-Ellison
syndromeà resulting in very high level of acidity and chronic gastric
ulcers

6. Secretin (HCO3-)
• Linear polypeptide (27aa), secreted by S cell of the duodenum and
jejunum.
• Primarily released on contact of S cell with gastric HCL.
• Not released until pH is < 4.5.
• FXN: Stimulates pancreatic bicarbonate secretion so that gastric HCL is
maintained ( neutralized) à optimum pH is maintained for the action of
pancreatic enzymes.
• It also inhibits gastric secretion
• Acts synergistically with CCK

7. Glucose dependent insulinotropic polypeptide
(GIP)
• Old name : Gastric inhibitory peptide (42 aa).
• Secreted by neuroendocrine K cells of duodenum and proximal jejunum.
• Stimulated by glucose, TG taken orally not IV.
üFxn:
• stimulates insulin release by hyperglycemia,
• inhibits gastric acid, pepsin and gastrin secretion ( OLD name)
• reduces gastric and intestinal motility;
• increase fluid and electrolyte secretion from small intestine.
• Overall regulates glucose and lipid metabolism by increasing release of
insulin.
• Response to GIP is defective in type 2 DM.

8. Vasoactive intestinal polypeptide ( VIP)
• Linear polypeptide (28 aa)
• is a neuropeptide released by enteric neurons.
• Present throughout the body but highest in nervous system and GUT.
• No evidence of its release during digestion
üFXN:
• Acts as neurotransmitter in central and autonomous nervous system,
• Vasodilation and relaxation of smooth muscle of GUT.
• Secretion of water and electrolytes from the pancreas and GUT as
well.
• Release of hormones from the hypothalamus, pancreas and GUT.

9. Glucagon like peptides ( GLP-1)
• Polypeptide (31aa)
• Site of origin: L cells in ileum and colon
ü FXN:
• It potentiates Glucose dependent insulin secretion
• Simple: Insulin production is 70% greater when when glucose is
administered orally than when similar conc is reached after IV.
• BUT WHY?
• This increment is due to intestinal factors, termed incretins ( most imp is
GLP1)à AUGMENTATION EFFECT
• USEFULALSO
• Good target for treating DMà increases the level of insulin significantly.
• GLP-2 acts as enterocyte-specific growth hormone.

10. Ghrelin
• Site of origin: stomach and hypothalamus
• 28 aa, acylated on ser3 with octanoic acid.
• Stimulates the release of GH ( so the name Growth-hormone release)
üFxn: Ghrelin stimulates to release neuropeptide Y (NPY)à NPY
enhances appetite (increases)
üREGUATED:
• Its production is increased by fasting, hypoglycemia and leptin.
• Conversely inhibited by food intake, hyperglycemia and obesity
• High before meal but falls rapidly after taking meal.

11. Somatostatin
• Secreted mainly by delta cells of pancreas, also by GUT and
hypothalamus.
• It is the main inhibitory peptide of GI tract.
• Fxn;
• Inhibits the production of numerous GUT peptides
• Like: gastrin, CCK, Secretin, VIP ,Insulin,
• Pancreatic enzymes and electrolytes into intestine

12. Other hormones

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