Transcript Hormones of the Gut

Hormones of the Gut
Beginning of
Endocrinology
• Bayliss and Starling--1902
– Acidification of denervated duodenum
or jejunum stimulated pancreatic
exocrine secretion.
– Injected extract of jejunal mucosa also
stimulated pancreatic exocrine
secretion.
– Postulated a humoral regulatory factor
they called “Secretin.”
– Secretin finally isolated in 1961.
Gut Regulatory Peptides
• Gut Nervous System
• Endocrine cells of
mucosa
– Basal secretory
granules
• Gut Peptides may be
– Hormones
• Travel to different organ
through blood stream.
– Paracrine
– Neurosecretory
• Neurotransmitters
Secretin
• 29 amino acid peptide
• Related to: glucagon, GIP, VIP, PHI,
PHM (Secretin family)
• Action:
– Stimulates Bicarbonate and Water
Secretion by Pancreas
Secretin Control
pH DUODENAL
LUMEN > 4.5
BICARBONATE
pH DODENAL
LUMEN < 4.5
ENDOCRINE
CELLS OF
MUCOSA
SECRETIN
PANCREAS
SOMATOSTATIN
Gastrin
• 1905, Edkins discovered that an
extract of gastric mucosa stimulated
acid secretion that he called Gastrin.
• 1960s, Gregory isolated and
sequenced Gastrin.
• 3 biologically active forms:
– “Big” = 34 amino acids
– ‘Little” = 17 amino acids
– “Mini” = 14 amino acids
Gastrin (Cont.)
• Structurally similar to Cholecystokinin:
– Gastrin-Cholecystokinin Family.
• Found in endocrine cells of gastric
antrum.
• Also identified in CNS.
• Stimulated by proteins and amino acids in
gastric lumen.
– Carbohydrates and Fats in effective.
• Somatostatin inhibits Gastrin release
Gastrin Action
• Stimulates Acid Secretion by Gastric
Mucosa
– May be due to stimulation of histamine
release by neighboring cells (paracrine)
• Stimulates growth of parietal cells of
the Gastric Mucosa
• Stimulates Mucosal blood flow
• Stimulates Pepsin Release
Gastrin Control
HIGH PROTEIN
MEAL
VAGUS (X)
GRP
SOMATOSTATIN
GASTRIN
MUCOSAL CELL
GASTRIN
ENTEROCHROMAFFIN HISTAMINE
CELL
HCl
PARIETAL
CELL
Cholecystokinin (CCK)
• 1928: Fat in small intestine stimulates the
gall bladder to contract--cholecystokinin.
• 1940s: Extract of duodenal mucosa
stimulates pancreas to secrete enzymes-pancreozymin.
• 1964-8: Purification of a single substance
that stimulated both contraction of the
gall bladder and pancreatic enzyme
secretion--settled on one name:
cholecystokinin (CCK).
Cholecystokinin
• Polypeptide found in different forms
including: 58, 39, 33, & 8 amino acids.
• 8 amino acid form has full biological
potency.
• Carboxy terminal 8 amino acids identical
in all forms.
• Larger forms may be prohormones.
• Preprocholecystokinin found: 115 amino
acids.
Cholecystokinin
• Located in duodenal and proximal
jejunal mucosa.
• Also found in CNS.
• Secretion stimulated by the presence
of intraduodenal protein or fat.
• May be a low molecular weight
CCK-releasing factor.
• Release is inhibited by somatostatin.
CCK Actions
• Stimulates contraction of gall
bladder, forcing bile into the
duodenum.
• Stimulates pancreatic enzyme
secretion.
• Trophic effects on pancreatic acini.
• Causes sphincter of Oddi to relax.
• Induces satiety.
CCK Control
FAT
SOMATOSTATIN
PROTEIN
CCK CELL
CCK
GALL
BLADDER
BILE RELEASE
PANCREATIC
ACINI
ENZYMES
Somatostatin
• 14 & 28 amino acid forms.
• Found in hypothalamus, throughout CNS
and Gut (including pancreas)
• Major inhibitory peptide of Gut. Inhibits
secretion of
– insulin
–
–
–
–
–
–
glucagon
CCK
secretin
gastrin
VIP
somatostatin (autocrine)
Somatostatin Control
PROTEIN
CHOLINERGIC
STIMULATION
FAT
STOMACH
ACID
SOMATOSTATIN
CELLS
SOMATOSTATIN
Other Peptides
• Vasoactive Intestinal Peptide (VIP)
– Neurotransmitter/neuroendocrine
– Relax esophageal and anal sphincter
– Increases blood flow in the gut
– Causes penile erection
• Gastrin-Releasing Peptide (GRP)
– Neurotransmitter/neuroendocrine
– Stimulates release of Gastrin
Other Peptides
• Substance P
– Neurotransmitter
– Stimulates Contraction of Smooth
Muscle
• Enkephalins
– Neurotransmitter
– Inhibits gut motility, antagonizes action
of Substance P
Ghrelin
• Produced by the stomach when
stomach is empty.
• Stimulates appetite
• Reduces metabolic rate
Peptide YY
• Produced by intestine in response to
being distended.
• Inhibits appetite.
• Increases metabolism.
Incretins
•
•
•
•
•
Glucagon Like Peptide-1 (GLP-1)
Produced by digestive tract.
Acts to give feeling of satiety
Inhibits gastric emptying
Inhibits glucose absorption from the
gut
• Increases insulin secretion
• Increases pancreatic β-cell mass
GLP-1