Hormones from the gastrointestinal tract
Glucagon-like peptide-1, GLP-1
GLP-1, glucagon-like peptide-1, is an anorectic polypeptide consisting of a single-chain of 30 amino acids, secreted by the digestive tract, mainly the ileum and the colon, secretion stimulated by food intake. The principal effect of the GLP-1 is to stimulate insulin secretion and to reduce glucagon secretion. In addition it inhibits gastric secretion and motility and, by hypothalamic action, it reduces appetite and food intake.
The administration of GLP- 1 in human beings induces decrease of food intake by slowing gastric emptying, giving a feeling of satiety, and by hypothalamic stimulation of receptors reduction of appetite. GLP-1 is inactivated by the dipeptidyl peptidase IV.
Among GLP-1 analogues, having its effects but a longer duration of action, currently under studies in human beings, one can quote liraglutide and exenatide.
Notice,
Oxyntomodulin is an anorectic polypeptide of 37 amino acids, derived from proglucagon, which decreases the appetite by activating the same receptors as GLP-1.
Gastric inhibitory polypeptide, GIP, also called dependant insulinotropic polypeptide, consisting of 42 amino acids, is secreted by the duodenum and the jejunum, especially after food intake. GIP stimulates insulin secretion and inhibits the acid secretion of the stomach.
The hormones produced by the gastrointestinal tract in response to food intake and which stimulate insulin secretion are called incretins. GLP-1 and GIP are incretins. Incretins were discovered from the observation that glucose taken by oral route elicited an insulin release more important than glucose which was administered by intravenous route.
Amylin
Amylin, a 37 amino acid peptide, is secreted into the circulation by pancreatic beta cells at the same time as insulin. Sulfonylureas stimulate both insulin and amylin secretion.
Amylin inhibits glucagon secretion, delays gastric emptying, reducing the feeling of hunger and has on the carbohydrate metabolism complex effects, sometimes opposed to those of insulin. In addition, amylin has a vasodilator effect similar to calcitonin.
Pramlintide is an amylin analogue, having amylin like properties, developed as an adjunct to insulin.
Ghrelin
Ghrelin, discovered by Japanese researchers in 1999, is an orexigenic polypeptide composed of 28 amino acids, secreted mainly by the stomach and, to a less degree, by various organs: intestine, pancreas, kidney, hypothalamus, pituitary gland.
Ghrelin secretion increases under fasting conditions and falls after food intake.
After gastrectomy, the concentration of ghrelin in plasma falls approximately 75%, which shows the importance of its secretion by the stomach.
Ghrelin is to be differentiated from GHRH, Growth Hormone Releasing Hormone, polypeptide of 44 amino acids, secreted by the hypothalamus. Both stimulate the synthesis and the release of growth hormone, GH, by the pituitary gland. But ghrelin has an orexigenic effect, i.e. it stimulates the appetite and increases dietary intake. It would act on the level of the hypothalamus by stimulating biosynthesis and secretion of neuropeptide Y and AgRP, Agouti-Related Protein.
Cholecystokinin, CCK
The name cholecystokinin was given to an unidentified compound, released by the duodenum, which elicited contractions of the gallbladder. Cholecystokinin was isolated much later and its chemical structure elucidated: it consists of polypeptides of 33, 8 or 4 amino acids resulting from hydrolysis of a protein of 115 amino acids. The corresponding cholecystokinins are called respectively CCK33, CCK8 and CCK4. Cholecystokinins are present in the digestive tract which releases them at the time of fat intake and in the brain, where one finds especially CCK8.
Cholecystokinin has an anorectic effect: it elicits an impression of satiety leading to a discontinuation of the dietary intake by transmitted peripheral action by vagal afferent nerves to the brain. It induces contractions of digestive fibers, in particular of gallbladder, increases pancreatic digestive secretions, it could stimulate cellular growth, in particular that of certain pancreatic tumors.
Cholecystokinin, present in the central nervous system in, has other not fully defined effects:
- modulation of painful perception; it inhibits antinociceptive effects of opioids and its antagonists reinforce them. So it could be involved in the development of the tolerance to morphine.
- anxiogenic effect: the intravenous injection of CCK4 elicits a syndrome of acute anxiety in human beings, simulating a panic attack .
- modulation of memorizing, the CCK8 could have an effect anti-amnestic and the CCK4 an amnestic effect.
The use of antagonists of cholecystokinin as anxiolytics is being considered.
Enterostatin
Enterostatin is an anorectic pentapeptide, formed in the lumen of the small intestine from the pancreatic procolipase under the influence of digestive enzymes. Enterostatin is also present in the gastric mucous membrane and certain parts of the brain.
Enterostatin reduces the dietary intake, in particular lipids and inhibits insulin secretion. It has peripheral and central effects (hypothalamic) acting indirectly by the vagal afferent nerves and directly. The beta subunit of the mitochondrial F1-ATPASE could be a receptor of enterostatin.
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