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The gastrointestinal hormones (or gut hormones) constitute a group of hormones secreted by enteroendocrine cells in the stomach, pancreas, and small intestine that control various functions of the digestive organs. Later studies showed that most of the gut peptides, such as secretin, cholecystokinin or substance P, were found to play a role of neurotransmitters and neuromodulators in the central and peripheral nervous systems. [1]
Enteroendocrine cells do not form glands but are spread throughout the digestive tract. They exert their autocrine and paracrine actions that integrate gastrointestinal function. [2]
The gastrointestinal hormones [3] can be divided into three main groups based upon their chemical structure.
Ghrelin is a peptide hormone released from the stomach and liver and is often referred to as the "hunger hormone" since high levels of it are found in individuals that are fasting. Ghrelin agonistic treatments can be used to treat illnesses such as anorexia and loss of appetites in cancer patients. Ghrelin treatments for obesity are still under intense scrutiny and no conclusive evidence has been reached. This hormone stimulates growth hormone release. Amylin controls glucose homeostasis and gastric motility
Glucose-dependent insulinotropic polypeptide possesses an acute influence on food intake through its effects on adipocytes
Oxyntomodulin plays a role in controlling acid secretion and satiation
Hormone or peptide | Molecular weight (Da) | Number of amino acids | Main gut localization | Principal physiologic actions |
---|---|---|---|---|
Gastrin family | ||||
Cholecystokinin | 3918 | 33 (also 385, 59) | Duodenum and jejunum, Enteric nerves | Stimulates gallbladder contraction and intestinal motility; stimulates secretion of pancreatic enzymes, insulin, glucagon, and pancreatic polypeptides; has a role in indicating satiety; the C-terminal 8 amino acid peptide cholecystokinin (CCK)-8 retains full activity |
Little gastrin | 2098 | 17 | Both forms of gastrin are found in the gastric antrum and duodenum | Gastrins stimulate the secretion of gastric acid, pepsinogen, intrinsic factor, and secretin; stimulate intestinal mucosal growth; increase gastric and intestinal motility |
Big gastrin | 3839 | 34 | ||
Secretin-glucagon family | ||||
Secretin | 3056 | 27 | Duodenum and jejunum | Stimulates pancreatic secretion of HCO3, enzymes and insulin; reduces gastric and duodenal motility, inhibits gastrin release and gastric acid secretion |
Vasoactive intestinal polypeptide (VIP) | 3326 | 28 | Enteric nerves | Relaxes smooth muscle of gut, blood vessels, and genitourinary system; increases water and electrolyte secretion from pancreas and gut; releases hormones from pancreas, gut, and hypothalamus |
Glucose-dependent insulinotropic | 4976 | 42 | Duodenum and jejunum | Stimulates insulin release; reduces gastric and intestinal motility; increases fluid and electrolyte secretion from small intestine |
Hormone or peptide | Major tissue locations in the gut | Principal known actions |
---|---|---|
Bombesin | Throughout the gut and pancreas | Stimulates release of cholecystokinin (CCK) and gastrin |
Calcitonin gene-related peptide | Enteric nerves | Unclear |
Chromogranin A | Neuroendocrine cells | Secretory protein |
Enkephalins | Stomach, duodenum | Opiate-like actions |
Enteroglucagon | Small intestine, pancreas | Inhibits insulin secretion |
Galanin | Enteric nerves | |
Ghrelin | Stomach | Stimulates appetite, increases gastric emptying |
Glucagon-like peptide 1 | Pancreas, ileum | Increases insulin secretion |
Glucagon-like peptide 2 | Ileum, colon | Enterocyte-specific growth hormone |
Growth factors | Throughout the gut | Cell proliferation and differentiation |
Growth hormone-releasing factor | Small intestine | Unclear |
Leptin | Stomach | Appetite control |
Motilin | Throughout the gut | Increases gastric emptying and small bowel motility |
Neuropeptide Y | Enteric nerves | Regulation of intestinal blood flow |
Neurotensin | Ileum | Affects gut motility; increases jejunal and ileal fluid secretion |
Pancreatic polypeptide | Pancreas | Inhibits pancreatic and biliary secretion |
Peptide YY | Colon | Inhibits food intake |
Somatostatin | Stomach, pancreas | Inhibits secretion and action of many hormones |
Substance P | Enteric nerves | Unclear |
Trefoil peptides | Stomach, intestine | Mucosal protection and repair |
Digestion is the breakdown of large insoluble food compounds into small water-soluble components so that they can be absorbed into the blood plasma. In certain organisms, these smaller substances are absorbed through the small intestine into the blood stream. Digestion is a form of catabolism that is often divided into two processes based on how food is broken down: mechanical and chemical digestion. The term mechanical digestion refers to the physical breakdown of large pieces of food into smaller pieces which can subsequently be accessed by digestive enzymes. Mechanical digestion takes place in the mouth through mastication and in the small intestine through segmentation contractions. In chemical digestion, enzymes break down food into the small compounds that the body can use.
Secretin is a hormone that regulates water homeostasis throughout the body and influences the environment of the duodenum by regulating secretions in the stomach, pancreas, and liver. It is a peptide hormone produced in the S cells of the duodenum, which are located in the intestinal glands. In humans, the secretin peptide is encoded by the SCT gene.
Cholecystokinin is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein. Cholecystokinin, formerly called pancreozymin, is synthesized and secreted by enteroendocrine cells in the duodenum, the first segment of the small intestine. Its presence causes the release of digestive enzymes and bile from the pancreas and gallbladder, respectively, and also acts as a hunger suppressant.
Gastrin is a peptide hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas.
Gastric acid, gastric juice, or stomach acid is a digestive fluid formed within the stomach lining. With a pH between 1 and 3, gastric acid plays a key role in digestion of proteins by activating digestive enzymes, which together break down the long chains of amino acids of proteins. Gastric acid is regulated in feedback systems to increase production when needed, such as after a meal. Other cells in the stomach produce bicarbonate, a base, to buffer the fluid, ensuring a regulated pH. These cells also produce mucus – a viscous barrier to prevent gastric acid from damaging the stomach. The pancreas further produces large amounts of bicarbonate and secretes bicarbonate through the pancreatic duct to the duodenum to neutralize gastric acid passing into the digestive tract.
Ghrelin is a hormone produced by enteroendocrine cells of the gastrointestinal tract, especially the stomach, and is often called a "hunger hormone" because it increases the drive to eat. Blood levels of ghrelin are highest before meals when hungry, returning to lower levels after mealtimes. Ghrelin may help prepare for food intake by increasing gastric motility and stimulating the secretion of gastric acid.
Satiety is a state or condition of fullness gratified beyond the point of satisfaction, the opposite of hunger. Following satiation, satiety is a feeling of fullness lasting until the next meal. When food is present in the GI tract after a meal, satiety signals overrule hunger signals, but satiety slowly fades as hunger increases.
Digestive enzymes are a group of enzymes that break down polymeric macromolecules into their smaller building blocks, in order to facilitate their absorption into the cells of the body. Digestive enzymes are found in the digestive tracts of animals and in the tracts of carnivorous plants, where they aid in the digestion of food, as well as inside cells, especially in their lysosomes, where they function to maintain cellular survival. Digestive enzymes of diverse specificities are found in the saliva secreted by the salivary glands, in the secretions of cells lining the stomach, in the pancreatic juice secreted by pancreatic exocrine cells, and in the secretions of cells lining the small and large intestines.
Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood-glucose–dependent mechanism.
Motilin is a 22-amino acid polypeptide hormone in the motilin family that, in humans, is encoded by the MLN gene.
Gastrinomas are neuroendocrine tumors (NETs), usually located in the duodenum or pancreas, that secrete gastrin and cause a clinical syndrome known as Zollinger–Ellison syndrome (ZES). A large number of gastrinomas develop in the pancreas or duodenum, with near-equal frequency, and approximately 10% arise as primary neoplasms in lymph nodes of the pancreaticoduodenal region.
Pancreatic polypeptide (PP) is a polypeptide secreted by PP cells in the endocrine pancreas. It regulates pancreatic secretion activities, and also impacts liver glycogen storage and gastrointestinal secretion. Its secretion may be impacted by certain endocrine tumours.
P/D1 cells are cells lining the fundus of the human stomach that produce ghrelin. Removal of these cells in gastric bypass surgery has a profound impact on later appetite regulation. These cells have also been shown to produce ghrelin's antagonistic hormone leptin. PD/1 cells are equivalent to A-like cells in rats and X-type cells in dogs. These endocrine cells can be microscopically distinguished from other gastric endocrine cells through their round, compact, electron-dense secretory granules.
Somatostatinomas are a tumor of the delta cells of the endocrine pancreas that produces somatostatin. Increased levels of somatostatin inhibit pancreatic hormones and gastrointestinal hormones. Thus, somatostatinomas are associated with mild diabetes mellitus, steatorrhoea and gallstones, and achlorhydria. Somatostatinomas are commonly found in the head of pancreas. Only ten percent of somatostatinomas are functional tumours [9], and 60–70% of tumours are malignant. Nearly two-thirds of patients with malignant somatostatinomas will present with metastatic disease.
Enteroendocrine cells are specialized cells of the gastrointestinal tract and pancreas with endocrine function. They produce gastrointestinal hormones or peptides in response to various stimuli and release them into the bloodstream for systemic effect, diffuse them as local messengers, or transmit them to the enteric nervous system to activate nervous responses. Enteroendocrine cells of the intestine are the most numerous endocrine cells of the body. They constitute an enteric endocrine system as a subset of the endocrine system just as the enteric nervous system is a subset of the nervous system. In a sense they are known to act as chemoreceptors, initiating digestive actions and detecting harmful substances and initiating protective responses. Enteroendocrine cells are located in the stomach, in the intestine and in the pancreas. Microbiota play key roles in the intestinal immune and metabolic responses in these enteroendocrine cells via their fermentation product, acetate.
Gastrointestinal physiology is the branch of human physiology that addresses the physical function of the gastrointestinal (GI) tract. The function of the GI tract is to process ingested food by mechanical and chemical means, extract nutrients and excrete waste products. The GI tract is composed of the alimentary canal, that runs from the mouth to the anus, as well as the associated glands, chemicals, hormones, and enzymes that assist in digestion. The major processes that occur in the GI tract are: motility, secretion, regulation, digestion and circulation. The proper function and coordination of these processes are vital for maintaining good health by providing for the effective digestion and uptake of nutrients.
The basal or basic electrical rhythm (BER) or electrical control activity (ECA) is the spontaneous depolarization and repolarization of pacemaker cells known as interstitial cells of Cajal (ICCs) in the smooth muscle of the stomach, small intestine, and large intestine. This electrical rhythm is spread through gap junctions in the smooth muscle of the GI tract. These pacemaker cells, also called the ICCs, control the frequency of contractions in the gastrointestinal tract. The cells can be located in either the circular or longitudinal layer of the smooth muscle in the GI tract; circular for the small and large intestine, longitudinal for the stomach. The frequency of contraction differs at each location in the GI tract beginning with 3 per minute in the stomach, then 12 per minute in the duodenum, 9 per minute in the ileum, and a normally low one contraction per 30 minutes in the large intestines that increases 3 to 4 times a day due to a phenomenon called mass movement. The basal electrical rhythm controls the frequency of contraction but additional neuronal and hormonal controls regulate the strength of each contraction.
The nervous system, and endocrine system collaborate in the digestive system to control gastric secretions, and motility associated with the movement of food throughout the gastrointestinal tract, including peristalsis, and segmentation contractions.
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The human digestive system consists of the gastrointestinal tract plus the accessory organs of digestion. Digestion involves the breakdown of food into smaller and smaller components, until they can be absorbed and assimilated into the body. The process of digestion has three stages: the cephalic phase, the gastric phase, and the intestinal phase.