Gastric Secretion and

Its RegulationPart II

Learning Objectives ….

•Gastric Hormones•Pancreatic secretions• Intestinal secretions•Regulation

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.

Gastrin

Source:• Produced by G cells in the stomach located mainly in antral region

with apex projecting towards the lumen.

•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.

Products of protein digestion (peptides and amino acids)

Vagal stimulationReleasing 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

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)

Cholecystokinin

Source:

• Produced by I cells of the small intestine.

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.

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

(+)

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.

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.

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)

(-)

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.

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.

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.

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

• 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

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.

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.

Leptin

secreted :

• Adipocytes

• the chief cells of the stomach

• Placenta,

• Breast milk.

• Blood leptin levels reflect total body fat stores.

• Reduce food intake.

• 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.

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.

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.

Pancreatic Secretions

• Bicarbonate • Enzymes (amylase, trypsin, chymotrypsin, elastase,

carboxypeptidase, A and B, lipase, colipase, cholesterol esterase, phospholipase, ribonuclease)

Regulation:i. Hormones: Secretin and CCKii. Neural : Parasympathetic and sympathetic

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, lactaseEnterokinase, dipeptidyl peptidase, aminopeptidase

What we learned ….

•Gastric Hormones•Pancreatic secretions• Intestinal secretions•Regulation

THANK YOU