GI Endocrinology

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What type of cell secretes Gastrin?

G cell

Where do you find G cells primarily?

In the Gastric Antrum and the Duodenum

What are the receptors for Gastrin and where are they located?

CCK1R and CCK2R.
Located in the brain, stomach, and SI

How many times does Gastrin cross the membrane?

7

What nucleotide does Gastrin associate with for its action?

Associates with Gq to activate Phospholipase C and DAG to stimulate Ca++

What is the action of Gastrin?

Stimulates:
-gastric acid secretion.
-parietal cells directly
-Enterochromaffin like cells that secrete histmine.
-Histidine decarboxylase to increase formation of histamine.
-Promotes stomach contractility

-Stimulates produciton and maintenance of gastric mucosa.

What is the cause of excess Gastrin and how does it effect the GI system?

G cell tumors can cause an excessive prod. of acid, hypertrophy of the mucosa, and extensive ulcers.

What is Zollinger-Ellison Syndrome?

Tumors of G cells in the pancreas and other places.

What stimulates the release of Gastrin?

-Vagus nerve by the smell or thought of food which releases GRP (Gastrin Releasing Peptide).
-Distension of the stomach causes mechanoreceptors to signal G cells.
-a.a and proteins in the stomach
-Calcium

What inhibits the release of Gastrin?

Chyme enters the Duodenum which senses the acid and causes the release of somatostatin to inhibit Gastrin release and limit acid production.

What cells produce Cholecystokinin (CCK)?

I cells

Where are I cells located?

Duodenum and Jejunum

Where is CCK cleared out of the body?

Kidney

What enzyme is necessary for CCK function?

Tyrosine Sulfate

What stimulates CCK?

-Lipids in the Duodenum primarily.
-CCK releasing factors.

What inhibits CCK?

Bile salts in the intestinal lumen

What is the receptor for CCK?

CCKR1
Increases Ca level in the target cell.

What are the effects of CCK?

-Contracts the Gall Bladder to relax the sphincter of Oddi and release Bile.
-Stimulates the Vagus nerve to stimulate secretion of digestive enzymes from the Pancreas.
-Also a neurotransmitter and stimulates satiety in the Hypothalamus.
-Inhibits acid prod. in stomach
-Stimulates prod. of somatostatin to lower acidity.
-delays gastric emptying and slows motility

Where is Histamine stored?

In the Enterochromaffin-like cells in the Gastric mucosa.

What causes the release of Histamine?

Gastrin

What are the receptors for Histamine?

H2 Histamine receptors.

How many times does histamine cross the membrane?

7 times

What is the action of Histamine?

Stimulates Gs to increase cAMP to release acid in the stomach.

What inhibits Histamine?

Anti-histamines

What cell types secrete Somatostatin?

Delta cell in the Pancreatic Islets
D cells throughout the stomach and intestines

What is the function of Somatostatin?

Inhibits the release of Gastrin and Gastric Acid. Modulates the digestive response and prevents overproduction of acid.

Where else can you find Somatostatin besides the GI tract?

Hypothalamus

What are the two forms of Somatostatin? (How many a.a?)

1. 14 a.a
2. 28 a.a

What is the receptor for Somatostatin and what is the method of action?

5 Isoforms
Associates with different G proteins depending on the location.

What is the stimulus for Somatostatin?

Acidic pH in the chyme

What cells produce Secretin and where do you find them?

S cells in the Duodenum and Jejunum

What stimulates the S cells?

low pH or chyme

What is the function of Secretin?

Stimulates the release of bicarbonate from the Pancreas

What is the mechanism of action of Secretin?

Acts on Gs to increase cAMP
Stimulates the activity of the Na/HCO3 co-transporter and the Cl/HCO3 exchanger across the Pancreatic Ductile cells.
Activate the chloride channel.

What other type of cell does Secretin stimulate?

D cells to release somatostatin to inhibit Gastrin.

What type of cells secrete Gastric Inhibitory Peptide (GIP) and where do you find these cells?

K cells of the duodenum and Jejunum

What stimulates the release of GIP?

Released after a carb and fat rich meal.
-Glucose, galactose, sweetness on the tongue.

What cells does GIP target?

Beta cells of the Pancreatic Islets and only operates when plasma glucose is above fasting levels.

What hormone does GIP stimulate the secretion of?

Insulin
-jejunal glucose (orally) is more effective in raising insulin than IV glucose.

What degrades GIP?

Lack of sugars in the SI and DPP IV (Dipeptidyl Peptidase).

Where do you find Motilin?

In the brain and the GI

What do the receptors for Motilin couple to?

Gq

What are the effects of Motilin?

Migrating Motility Complex: stomach is empty for 90 minutes then you get 10 minutes of contractions due to Motilin.
Also stimulates enzyme secretion by the stomach and pancreas and gallbladder contractions.
clearing the leftovers when fasting.

What cells secrete Ghrelin?

X/A cells of the Oxyntic Mucosa, small and large intestine and pancreas.

What is the function of Ghrelin?

Helps regulate GH secretion.
Effects GI similar to Motilin

What cell type secretes Neurotensin and where are they found?

N cells in the Jejunum and Ileum

What stimulates the release of Neurotensin?

Fatty acids in the intestine

What is the receptor for neurotensin?

NTR1 associated with Gq -> IP3/DAG

What are the functions of neurotensin?

Inhibits gastric acid secretion, slows gastric emptying, decrease motility of SI, Increase motility of Colon, aids fat digestion and absorption, stimulates uptake of bile acids by Ileum and return to hepatocytes, stimulates bile secretion.

What cells produce Pancreatic Polypeptides (PPP)?

F cells in the pancreatic islet

What is the stimulation of PPP?

Plasma concentration increases with eating. Can be stimulated by chewing. Increases when stomach is distended but also when it is not.

What is the function of PPP?

part of the Ileal Brake Mechanism: slows motility and increases feeling of satiety.

What cell produces GLP 1 and GLP 2?

L cells in the SI, Colon, Distal Ileum

What stimulates GLP 1?

eating

What is the function of GLP 1?

-Incretin: stimulates insulin secretion and inhibits glucagon secretion.
-Slows gastric emptying by relaxing smooth muscle in pylorus.
-Inhibits food intake though hypothalamus and brainstem appetite centers.

What is the function of GLP 2?

-Stimulates growth of intestinal mucosa
-Stimulates glucose and a.a transport in mucosa
-Reduces inflammation.
-Ileal Brake Mechanism: slows gastric and pancreatic exocrine secretion and slows stomach emptying and GI motility in response to nutrients in the ileum, Mostly due to fatty acid.

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