Hormones of the Gut

• All of them are peptides.
• Many of them are also found in other tissues, especially the brain.
• Many act in a paracrine manner as well as being carried in the blood as true hormones.
• Their importance to health is uncertain as no known deficiency disorders have been found for any of them.

• gastrin
• somatostatin
• secretin
• cholecystokinin (CCK)
• ghrelin
• obestatin
• neuropeptide Y (NPY)
• peptide YY_3-36 (PYY_3-36)

Gastrin

• Gastrin is a mixture of several peptides, of which the most active contains 14 amino acids.
• It is secreted by cells in the stomach and duodenum
• It stimulates the exocrine cells of the stomach to secrete gastric juice, a mixture of
  • hydrochloric acid and
  • the proteolytic enzyme pepsin.

Somatostatin

• the stomach (thus a paracrine effect) where it inhibits the release of gastrin and hydrochloric acid
• the duodenum where it inhibits the release of secretin and cholecystokinin
• the pancreas where it inhibits the release of glucagon.

Taken together, all of these actions lead to a reduction in the rate at which nutrients are absorbed from the contents of the intestine.

Secretin

• It is a polypeptide of 27 amino acids.
• It is secreted by cells in the duodenum when they are exposed to the acidic contents of the emptying stomach.
• It stimulates the exocrine portion of the pancreas to secrete bicarbonate into the pancreatic fluid (thus neutralizing the acidity of the intestinal contents).

Cholecystokinin (CCK)

• A mixture of peptides, of which an octapeptide (8 amino acids) is the most active.
• It is secreted by cells in the duodenum and jejunum when they are exposed to food.
• It acts
  • on the gall bladder stimulating it to contract and force its contents of bile into the intestine
  • on the pancreas stimulating the release of pancreatic digestive enzymes into the pancreatic fluid.
• CCK also acts on vagal neurons leading back to the medulla oblongata which give a satiety signal (i.e., "that's enough food for now").

Ghrelin and Obestatin

Ghrelin

• is secreted by endocrine cells in the stomach, especially when one is hungry;
• acts on the hypothalamus to stimulate feeding;
• This action counteracts the inhibition of feeding by leptin, PYY_3-36, and obestatin.

Obestatin

This peptide of 23 amino acids is cut from the same precursor molecule from which ghrelin is generated. But its effects — at least in rats and mice — are just the reverse of those of ghrelin.

Presumably, the cutting of each precursor molecule (a peptide of 117 amino acids) yields one molecule of each hormone so one might expect their effects to cancel out. However, each hormone must receive further chemical modification to be active and perhaps controlling this permits one or the other to dominate under the appropriate conditions.

Neuropeptide Y (NPY)

Neuropeptide Y (which is also secreted by neurons in the hypothalamus) contains 36 amino acids. It is a potent feeding stimulant and causes increased storage of ingested food as fat.

PYY_3-36

Peptide YY_3-36 contains 34 amino acids, many of them in the same positions as those in neuropeptide Y.

It is released by cells in the intestine after meals. The amount secreted increases with the number of calories that were ingested.

• the hypothalamus to suppress appetite;
• the pancreas to increase its exocrine secretion of digestive juices;
• the gall bladder to stimulate the release of bile.