1. Hormones of the Gut

2. 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.

3. 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

4. Secretin 29 amino acid peptide
Related to: glucagon, GIP, VIP, PHI, PHM (Secretin family)
Action:
Stimulates Bicarbonate and Water Secretion by Pancreas

5. Secretin Control pH DUODENAL LUMEN > 4.5 pH DODENAL LUMEN < 4.5
BICARBONATE
ENDOCRINE
CELLS OF
MUCOSA
SOMATO-
STATIN
GLUCAGON
PANCREAS

6. 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

7. 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

8. 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

9. Gastrin Control HIGH PROTEIN MEAL VAGUS (X) GRP SOMATO- STATIN GASTRIN
MUCOSAL CELL
GASTRIN
HCl
ENTERO-
CHROMAFFIN
CELL
PARIETAL
CELL
HISTAMINE

10. 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).

11. 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.

12. 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.

13. 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.

14. CCK Control FAT PROTEIN SOMATOSTATIN CCK CELL CCK GALL BLADDER
PANCREATIC
ACINI
BILE RELEASE
ENZYMES

15. 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)

16. Somatostatin Control STOMACH ACID PROTEIN FAT CHOLINERGIC STIMULATION
CELLS
SOMATOSTATIN

17. 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)
Stimulates release of Gastrin

18. Other Peptides Substance P Enkephalins Neurotransmitter
Stimulates Contraction of Smooth Muscle
Enkephalins
Inhibits gut motility, antagonizes action of Substance P

19. Ghrelin Produced by the stomach when stomach is empty.
Stimulates appetite
Reduces metabolic rate

20. Peptide YY Produced by intestine in response to being distended.
Inhibits appetite.
Increases metabolism.

21. 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

22. GLP-1