Gastric secretion and its regulation involves many hormones. Gastrin stimulates gastric acid secretion from parietal cells. Cholecystokinin stimulates gallbladder contraction and pancreatic enzyme secretion. Secretin increases pancreatic bicarbonate and bile secretion. Somatostatin broadly inhibits gastric acid, pancreatic enzyme and bile secretion. VIP increases intestinal secretion and blood flow. GIP and motilin regulate gastric emptying and intestinal motility.
3. GI Hormones are broadly classified into 3 categories:
I. Gastrin family that includes cholecystokinin and gastrin.
II. Secretin family that includes GIP, Glucagon, secretin and VIP
III. Other polypeptides.
4. Gastrin
Source:
• Produced by G cells in the stomach located mainly in antral region
with apex projecting towards the lumen.
5. • Major hormone that stimulates gastric acid secretion.
• Gastrin G34 and G17,- two major forms of gastrin.
• Most gastrin in the circulation during fasting is G34, whereas after
a meal it is G17.
• Antral G cells are primary source of G17, whereas duodenal G cells
are primary source of G-34.
• Metabolized: kidney (primarily), intestine and liver.
6. Products of protein digestion
(peptides and amino acids)
Vagal stimulation
Releasing GRP
Food in stomach
(gastric distension)
G cells of stomach
Secretion of gastrin
Parietal cells of stomach
HCl Secretion
High acidic gastric content
(autoregulation of gastrin
secretion)
Acidic duodenal chyme
(secretes hormones)
Intestinal hormones
(GIP,VIP,, Somatostatin,
secretin and glucagon)
(-)(-)
(-)
Control of HCl Secretion
7. 2. Tropic action
3. Stimulates gastric motility
4. Stimulates insulin secretion and exocrine pancreatic secretion.
5. Colonic contraction that initiates gastrocolic reflex after a meal, thus
activating defecation after meal.
6. Stimulates histamine secretion of ECL (enterochromaffin like cells)
9. Functions
• Contraction of Gall Bladder.
• Stimulates pancreatic secretion rich in enzymes.
• Relaxation of Sphincter of Oddi
• Augments the action of Secretin to produce alkaline pancreatic secretion.
• Inhibits gastric acid secretion and gastric motility delays gastric emptying.
• Stimulates growth of pancreas.
• Enhances motility of small intestine and colonic movement.
• In brain, acts as anorexigenic neurotransmitter i.e inhibits food intake.
10. Regulation :
Cholecystokinin
Contact of intestinal mucosa with fatty acids and peptides
Stimulation of I cells
Secretion of CCK
Increased release of bile and pancreatic secretion
Digestion of protein and fat
Fatty acids and peptides
Positive
feedback
(+)
11. Secretin
First hormone to be discovered
• Selectively expressed in specialized enteroendocrine cells of the
small intestine called S cells
• Mechanism of action:
secretin acts on adenylate cyclase on the cell membrane and
increases cytosolic formation of cAMP.
12. Functions
1. It increases secretion of pancreatic juice rich on bicarbonate.
2. It also increases alkaline bile secretion.
3. Augments the action of CCK to produce pancreatic secretion rich in
enzymes.
4. Decreases gastric acid secretion and motility.
5. Causes contraction of pyloric sphincter.
13. Regulation of
secretin
Contact of intestinal mucosa with acidic chyme and peptides
Stimulation of S cells
Secretion of secretin
Stimulation of pancreatic secretion rich in water and bicarbonate
H2O AND HCO3 floods duodenum
Neutralization of acid in duodenum(increase duodenal pH)
(-)
14. Glucagon
• Synthesized and released from pancreatic alpha cells and from
intestinal L cells of the ileum and colon.
• Glucagon is released from pancreas in response to a meal and
binds to G protein–coupled receptors on skeletal muscle and the
liver to exert its glucoregulatory effects.
• Regulates glucose homeostasis via gluconeogenesis,
glycogenolysis, and lipolysis and is counter regulatory to insulin.
15. Somatostatin
• Found in almost every organ in the body and throughout the GI
tract.
• In the gut, somatostatin is produced by
• D cells in the gastric and intestinal mucosa
• islets of the pancreas,
• enteric neurons.
16. Somatostatin has broad inhibitory actions:
• Reduces gastric acid production and pepsinogen secretion
• Inhibits pancreatic enzyme, fluid, and bicarbonate secretion and
reduces bile flow.
• Its effects on gut motility are largely inhibitory
• Reduces intestinal transport of nutrients and fluid,
• Inhibitory effects on tissue growth and proliferation.
17. Vasoactive Intestinal Polypeptide (VIP)
• VIP secreted from mucosal cells of entire GIT
• Found in nerves of GIT, other autonomic nerves, blood and also
in brain.
• VIP is a potent vasodilator that
• Increases blood flow in the GI tract
• Smooth muscle relaxation
18. • Markedly increases intestinal secretion rich in electrolytes and water; in excess
produces watery diarrhea.
• Decreases GI motility.
• neuromodulator of sphincters of the GI tract:
• LES
• Sphincter of Oddi
19. Glucose-dependent Insulinotropic Polypeptide (GIP)
• K cells present in the mucosa of duodenum and jejunum.
• Inhibits gastric secretion and motility: Gastric inhibitory peptide (GIP).
• Stimulates insulin secretion.
20. Motilin
• Endocrine cells of the duodenal epithelium.
• Contraction of intestinal smooth muscle increases GI motility,
esp in interdigestive phase.
• It is a major regulator of migrating motor complex(MMC) that
sweeps and cleans the intestine and thus, prepares the intestine
for next meal.
21. Leptin
secreted :
• Adipocytes
• the chief cells of the stomach
• Placenta,
• Breast milk.
• Blood leptin levels reflect total body fat stores.
• Reduce food intake.
22. • Leptin's ability to reduce food intake occurs within the brain
• Decreasing NPY a potent stimulant of food intake
• Increasing (α−MSH), an inhibitor of food intake.
• Peripherally, leptin acts synergistically with cholecystokinin to
reduce meal size.
23. Ghrelin
gastric fundus
• Intestine
• Pancreas
• Pituitary
• Kidney
• Placenta.
• Strong orexigenic that play a central role in the neurohormonal
regulation of food intake and energy homeostasis.
24. Guanylin
• Paneth cells (endocrine cells: crypts of Lieberkuhn of small
intestine)
• Stimulate guanylyl cyclase increase conc. of cGMP increases
activity of chloride channels increases chloride secretion into
the intestine regulates fluid movement across intestinal tract.
25.
26. Pancreatic Secretions
• Bicarbonate
• Enzymes (amylase, trypsin, chymotrypsin, elastase,
carboxypeptidase, A and B, lipase, colipase, cholesterol
esterase, phospholipase, ribonuclease)
Regulation:
i. Hormones: Secretin and CCK
ii. Neural : Parasympathetic and sympathetic
27. Intestinal secretions
• Villi
• Microvilli: 1) Increase surface area,
2) Seat for attachment of enzymes
for terminal digestion of CHO+proteins
3) Stirring mechanism
Brush Border Enzymes:
Maltase, dextrinase, lactase
Enterokinase, dipeptidyl peptidase, aminopeptidase
28. What we learned ….
•Gastric Hormones
•Pancreatic secretions
•Intestinal secretions
•Regulation
Apical surface of G cells contains numerous microvilli containing receptors for chemicals that mediate gastrin release.
Gastrin producing cells also present in hypothalamus, anterior pituitary, medulla, fetal pancreas and also in vagus and sciatic nerve(as neurotransmitter)
T ½- G34 amide is 30 minutes ,G17amide is 3-7 minutes.
Disease State:
Zollinger-Ellison syndrome: chronic hypergastrinemia that causes peptic ulcer.
Disease State:
Zollinger-Ellison syndrome: chronic hypergastrinemia that causes peptic ulcer.
Also present as neurotransmitter in cerebral cortex, somatic nerves and nerves of distal ileum and colon.
The secretin receptor is a member of a large family of G protein–coupled receptors (GPCRs)
The gene for glucagon encodes not only preproglucagon but also glucagon-like peptides (GLPs).
This precursor peptide consists of a signal peptide, a glucagon-related polypeptide, glucagon, and GLP-1 and GLP-2.
GLP-1 stimulates insulin secretion and augments the insulin-releasing effects of glucose on the pancreatic beta cell
GLP-1 analogs have been developed for the treatment of type II diabetes mellitus. A long-acting human GLP-1 analog improves beta cell function and can lower body weight in patients with type II diabetes.
GLP-2 is an intestinal growth factor and may have therapeutic implications in the maintenance of the GI mucosal mass and the reversal of villus atrophy.
14–amino acid cyclic peptide.
Found in almost every organ in the body and throughout the GI tract.
In the gut, somatostatin is produced by
D cells in the gastric and intestinal mucosa
islets of the pancreas,
enteric neurons.
Its effects on gut motility are largely inhibitory, with the exception that it stimulates the migrating motor complex, possibly through effects on motilin.
The inhibitory effects of somatostatin are mediated by
decrease in cAMP,
Ca2+ channel inhibition,
Somatostatin analogs are used to treat conditions of hormone excess produced by endocrine tumors, such as
Acromegaly
Carcinoid tumors
Islet cell tumors (including gastrinomas).
The inhibitory effects on secretion have been exploited by using somatostatin analogs to treat some forms of diarrhea and reduce fluid output from pancreatic fistulas.
or K+ channel opening.
The VIP receptor is a G protein–coupled receptor that stimulates intracellular cAMP generation.
Normally, serum VIP levels are low and do not appreciably change with a meal.
VIP, along with NO, is a primary component of nonadrenergic, noncholinergic nerve transmission in the gut.
Tumor of VIP secreting cells is called VIPoma. Profuse watery diarrhoea and hypotension are major features of VIPoma.
In certain pathologic conditions, such as achalasia and Hirschsprung's disease, the lack of VIP innervation is believed to play a major role in defective esophageal relaxation and bowel dysmotility, respectively
However, GLP 1 derived from glucagon appears to be more potent than GIP in promoting insulin secretion.
Motilin is a 22–amino acid peptide
Produced by endocrine cells of the duodenal epithelium.
It acts on G-protein coupled receptors on enteric neurons.
It causes contraction of intestinal smooth muscle and therefore, increases GI motility, especially in interdigestive phase.
It is a major regulator of migrating motor complex(MMC) that sweeps and cleans the intestine and thus, prepares the intestine for next meal.
Erythromycin, can be used in patients having hypomotility of GIT, as this antibiotic and its derivative bind to motilin receptors and facilitate intestinal motility.
Leptin is a 167–amino acid protein that is secreted primarily from
Adipocytes.
the chief cells of the stomach
Placenta,
Breast milk.
Blood leptin levels reflect total body fat stores.
Its primary action appears to be to reduce food intake.
Leptin effect on weight loss has been demonstrated in some clinical trials.
Leptin deficiency has been reported as a cause of obesity in a few families, but this condition is extremely rare.
Ghrelin is produced by distinctive endocrine cells known as P/D1 cells.
Ghrelin is a strong orexigenic that play a central role in the neurohormonal regulation of food intake and energy homeostasis.
Ghrelin released from the stomach acts on the vagus nerve to exert its effects on feeding.
At CNS level, ghrelin activates NPY, which is involved in the regulation of feeding.
When administered centrally or peripherally ghrelin
Stimulates growth hormone secretion,
Increases food intake, and Produces weight gain.
Stimulates gastric contraction and enhances stomach emptying (Motilin like)
increase
During fasting or
Conditions associated with negative energy balance, such as starvation or anorexia.
low
After eating
Obesity.
(hence called guanylin) thus increasing conc. of cGMP which increases activity of chloride channels and increases chloride secretion into the intestine and regulates fluid movement across intestinal tract.
Applied Physiology:
Enterotoxins of some strains of E.coli that cause diarrhea has structural similarity with guanylin causing fluid secretion into the intestinal lumen.
