GASTROINTESTINAL HORMONE

GASTROINTESTINAL HORMONE:

 

Introduction:

·         Gastrointestinal hormones are chemical messenger that regulate the physiological functions of the intestine and pancreas including secretion, motility, absorption and digestion. In addition to these well defined physiological effects, GI hormones can stimulate proliferation and the non-neoplastic intestinal mucosa and pancreas.

·         Gastrointestinal system is a collection of cells, tissues, organs and biochemical that allow for digestion and absorption of food into the body.

·         GI hormones are biological molecule which helps our body to digest and absorb the food that we eat.

·         Hormones are released from the endocrine cells in the stomach, pancreas and intestine which aid in digestion by stimulating the release of bile from the gall bladder and enzymes from the pancreas into the duodenum.

·         The classical GI hormones are secreted by epithelial cells lining the lumen of the stomach and small intestine. These hormone secreting cells- endocrinocytes are interspersed among a large number of epithelial cells that secrete their products into the lumen or take up nutrients from the lumen.

·         GI hormones are secreted into the blood and hence circulate chemically, where they affect function of other parts of the digestive tube, liver, pancreas, brain and a variety of other targets.

·         There are a bunch of hormones, neuropeptides and neurotransmitters that affect gastrointestinal function of number of classic GI hormones which are also synthesized in the brain and sometimes referred to as “brain gut peptide”.

There are following types of gastro-intestinal hormones are present that perform different functions:

1)      Gastrin:

·         Gastrin hormone was first postulated in 1906 by Edkins. The determination of the amino acid structure of gastrin followed its extraction from a solid tumor in 1964.

·         As we eat food, it moves from mouth to the oesophagous and down into the stomach. Some of the stomach’s cells release a hormone called gastrin.

·         Gastrin release is stimulated by food components particularly aromatic amino acid and its derivatives and is inhibited by luminal acid.

·         The secretion of gastrin is stimulated by food arriving in the stomach in response to eating food (especially protein), gastrin causes the stomach to produce more acid and stimulates contraction of muscles in the wall of part of the stomach; ileum and colon. The contraction propels food through the digestive tract.

·         Secretion of gastrin is inhibited by low pH.

·         Gastrin occurs in various molecular forms but all the biological activity resides in the HC- terminal amino acid. The major molecular form contain 17 (G17, 2098 Da), 14 (G14; pentagastrin) and 34 (G34, big gastrin) amino acid.

·         In humans gastrin is formed mainly in the gastric antrum where G17 predominates, but is also found in the upper small intestine, mainly as G34. These two are the pre-dominant circulating forms.

·         Gastrin is synthesized in G- cells, where it is stored in large electro-lucent forms.

·         Gastrin release following protein ingestion and gastric distensions stimulate gastric acid secretion and have a triple effect in the gastrin mucosa.

·         It also commands the stomach to stop making much acid.

·         Also helps in the release of bicarbonate from the bile ducts. Bicarbonate neutralizes the stomach acid that was just flushed into the duodenum from the stomach.

·         Gastrin tells the pancreas to start secreting bicarbonate juice.

·         Gastrin occurs in various molecular forms, but all the biological activity resides in the HC- terminal of amino acid. The major molecular form contains 17 (G17; 2098 Da), 14 (G14; pentagastrin) and 34 (G34, big gastrin) amino acid.

·         In human gastrin is formed mainly in the gastric antrum where G17 predominates, but is also found in the upper small intestine, mainly as G34. These two are predominates circulating forms.

·         Gastrin is synthesized in G- cells, where it is stored in large electro-lucent forms.

 

2)      CCK (Cholecystokinin):

·         It was described by Ivy and oldberg (1928) as a contaminant in impure secretin preparations.

·         Pancreas also secretes digestive enzymes which are guarded by GI hormone called CCK.

·         CCK is released by the cells of duodenum.

·         It also tell gall bladder to release a substance called bile, which is essential for digestion and absorption of fat.

·         CCK release is stimulated by fats, proteins and amino acid.

·         CCK produces by endocrine cells of the gut, the neurons of the brain and the peripheral nervous system of the GI tract.

3)      Secretin:

·         Discovery of secretin was first recognized by Baylise and Starling in 1902.

·         Secretin is a GI hormone that stimulates the secretion of water and bicarbonate from the pancreas and bile ducts whenever the stomach empties too much acid into the small intestine. Bicarbonate neutralizes the acid from the stomach.

·         Also increases the release of enzymes from the pancreas.

·         Secretin stimulates the secretion of bile in the liver.

·         Secretin is secreted in response to the fat in chyme.

·         Secretin is secreted by the lining of the duodenum in response to acid entering from the stomach.

 

4)      Gastric Inhibitory Peptide (GIP):

·         GIP is also known as Glucose dependent insulinotropic polypeptide.

·         GIP is the hormone that is present in the duodenum.

·         It decreases the stomach churning in order to slow the emptying of the stomach.

·         It also induces insulin secretion.

·         This hormone has two rules, first it tells the stomach to stop making stomach acid and to stop moving around so much it normally does to help mechanically digest your food  and pass it along into the intestine. Second GIP helps the pancreas release a hormone called insulin, which is the hormone that derives blood sugar into your body cells.

 

5)      Motilin:

·         Motilin is present in the duodenum.

·         It increases the migrating myoelectric complex component of GI motility and stimulates the production of pepsin.

·         A GI hormone that apparently participate in controlling smooth muscle contractions in the stomach and small intestine.

·         Any secretion of the GI mucosa affecting the timing and quantity of various digestive secretions or causing enhanced motility of the targeted organ.

 

6)      Ghrelin:

·         Studies on Ghrelin led to the identification of a specific co-protein coupled receptor termed the GH- secretogogue receptor. (GHSR)

·         Subsequently, the endogenous ligand for this receptor was accepted as an acetylated peptide of 28 amino acid, called Ghrelin, cleaved from a 117 amino acid precursor, preproghrelin- Ghrelin and motilin along with their receptors and precursors are structurally related, leading to the suggestions that they form a new family of peptide.

·         Ghrelin is circulating hormone secreted predominately from the oxyntic mucosa of the stomach but is found in other areas of the gut.

·         Its major action is to stimulate food intake.

·         It is only known as oxygenic hormone and it opposes the satiety signal.

 

 

7)      Somatostatin:

·         Somatostatin was initially isolated from the hypothalamus as 1640Da peptides of 14 amino acids that are inhibited by the release of growth hormone.

·         It is widely distributed throughout the central and peripheral nervous system.

·         It is found in variety of endocrine tissues.

 

8)      Vasoactive Intestinal Peptide (VIP):

·         It is a 3328Da peptide neurotransmitter which consists of 28amino acid.

·         It is widely distributed throughout the CNS and PNS.

·         Its highest concentration occurs in the submucosa of the intestinal tract, where it is found in postganglionic intrinsic nerves.

·         It is a potent stimulator                 of small intestinal and colonic enterocyte secretion of water and electrolytes, acting via elevation of c AMP.

·         Somatostatin  also perform some important functions like smooth muscle relaxation in the alimentary tract and in the systemic vasculature, stimulation of insulin release, counteracted by a direct glucagon like effect of VIP in stimulating hepatic gluconeogenesis and glycogenolysis.

·         Somatostatin helps in stimulation of pancreatic bicarbonate secretion and relaxation of gall bladder, pyloric sphincter and circular muscle of the small intestine with contraction of the longitudinal muscles.

 

9)      BBS/ GRP:

·         BBS, a tetra decapeptide originally isolated from the skin of the frog Bombina bombisa is analogous to mammalian GRP.

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