Enteroendocrine cell | |
---|---|
Details | |
System | Endocrine system |
Location | Gastrointestinal tract |
Identifiers | |
Latin | endocrinocyti gastroenteropancreatici |
MeSH | D019858 |
TH | H3.04.02.0.00024, H3.08.01.0.00003 |
FMA | 62930 |
Anatomical terms of microanatomy |
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. [1] [2] Enteroendocrine cells of the intestine are the most numerous endocrine cells of the body. [3] [4] [5] 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. [6] In a sense they are known to act as chemoreceptors, initiating digestive actions and detecting harmful substances and initiating protective responses. [7] [8] 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 (short chain fatty acid), acetate. [9]
Intestinal enteroendocrine cells are not clustered together but spread as single cells throughout the intestinal tract. [7]
Hormones secreted include somatostatin, motilin, cholecystokinin, neurotensin, vasoactive intestinal peptide, and enteroglucagon. [10] The enteroendocrine cells sense the metabolites from intestinal commensal microbiota and, in turn, coordinate antibacterial, mechanical, and metabolic branches of the host intestinal innate immune response to the commensal microbiota. [11]
K cells secrete gastric inhibitory peptide, an incretin, which also promotes triglyceride storage. [12] K cells are mostly found in the duodenum. [13]
L cells secrete glucagon-like peptide-1, an incretin, peptide YY3-36, oxyntomodulin and glucagon-like peptide-2. L cells are primarily found in the ileum and large intestine (colon), but some are also found in the duodenum and jejunum. [14]
I cells secrete cholecystokinin (CCK), and have the highest mucosal density in the duodenum with a decreasing amount throughout the small intestine. [15] They modulate bile secretion, exocrine pancreas secretion, and satiety. [16]
Stomach enteroendocrine cells, which release gastrin, and stimulate gastric acid secretion. [17]
Enterochromaffin cells are enteroendocrine and neuroendocrine cells with a close similarity to adrenomedullary chromaffin cells secreting serotonin. [18]
Enterochromaffin-like cells or ECL cells are a type of neuroendocrine cell secreting histamine.
Located in a increasing manner throughout the small intestine, with the highest levels found in the in ileum, [19] N cells release neurotensin, and control smooth muscle contraction. [20]
S cells secrete secretin mostly from the duodenum, but also in decreasing amounts throughout the rest of the small intestine, [21] and stimulate exocrine pancreatic secretion. [16]
Also called Delta cells, D cells secrete somatostatin.
Gastric enteroendocrine cells are found in the gastric glands, mostly at their base. The G cells secrete gastrin, post-ganglionic fibers of the vagus nerve can release gastrin-releasing peptide during parasympathetic stimulation to stimulate secretion. Enterochromaffin-like cells are enteroendocrine and neuroendocrine cells also known for their similarity to chromaffin cells secreting histamine, which stimulates G cells to secrete gastrin.
Other hormones produced include cholecystokinin, somatostatin, vasoactive intestinal peptide, substance P, alpha and gamma-endorphin. [10] [24]
Pancreatic enteroendocrine cells are located in the islets of Langerhans and produce most importantly the hormones insulin and glucagon. The autonomous nervous system strongly regulates their secretion, with parasympathetic stimulation stimulating insulin secretion and inhibiting glucagon secretion and sympathetic stimulation having opposite effect. [25]
Other hormones produced include somatostatin, pancreatic polypeptide, amylin and ghrelin.
Rare and slow growing carcinoid and non-carcinoid tumors develop from these cells. When a tumor arises it has the capacity to secrete large volumes of hormones. [2] [26]
The very discovery of hormones occurred during studies of how the digestive system regulates its activities, as explained at Secretin § Discovery .
In rats ( Rattus rattus ) the short-chain fatty acid receptor GPR43 is expressed both by this cell type and by mast cells of the mucosa. [27]
The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e., it has both an endocrine and a digestive exocrine function. 99% of the pancreas is exocrine and 1% is endocrine. As an endocrine gland, it functions mostly to regulate blood sugar levels, secreting the hormones insulin, glucagon, somatostatin and pancreatic polypeptide. As a part of the digestive system, it functions as an exocrine gland secreting pancreatic juice into the duodenum through the pancreatic duct. This juice contains bicarbonate, which neutralizes acid entering the duodenum from the stomach; and digestive enzymes, which break down carbohydrates, proteins and fats in food entering the duodenum from the stomach.
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.
Delta cells are somatostatin-producing cells. They can be found in the stomach, intestine and the pancreatic islets. Delta cells comprise ca 5% of the cells in the islets but may interact with many more islet cells than suggested by their low numbers. In rodents, delta-cells are located in the periphery of the islets; in humans the islet architecture is generally less organized and delta-cells are frequently observed inside the islets as well. In both species, the peptide hormone Urocortin III (Ucn3) is a major local signal that is released from beta cells to induce the local secretion of somatostatin. It has also been suggested that somatostatin may be implicated in insulin-induced hypoglycaemia through a mechanism involving SGLT-2 receptors. Ghrelin can also strongly stimulate somatostatin secretion, thus indirectly inhibiting insulin release. Viewed under an electron microscope, delta-cells can be identified as cells with smaller and slightly more compact granules than beta cells.
Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones. Somatostatin inhibits insulin and glucagon secretion.
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 1.5 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.
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.
Glucose-dependent insulinotropic polypeptide, abbreviated as GIP, is an inhibiting hormone of the secretin family of hormones. While it is a weak inhibitor of gastric acid secretion, its main role, being an incretin, is to stimulate insulin secretion.
Motilin is a 22-amino acid polypeptide hormone in the motilin family that, in humans, is encoded by the MLN gene.
Enteroglucagon is a peptide hormone derived from preproglucagon. It is a gastrointestinal hormone, secreted from mucosal cells primarily of the colon and terminal ileum. It consists of 37 amino acids. Enteroglucagon is released when fats and glucose are present in the small intestine; which decrease the motility to allow sufficient time for these nutrients to be absorbed.
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.
Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption. The initial product GLP-1 (1–37) is susceptible to amidation and proteolytic cleavage, which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1 protein secondary structure includes two α-helices from amino acid position 13–20 and 24–35 separated by a linker region.
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.
The gastrointestinal 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.
The enterogastric reflex is one of the three extrinsic reflexes of the gastrointestinal tract, the other two being the gastroileal reflex and the gastrocolic reflex. The enterogastric reflex is stimulated by duodenal distension. It can also be stimulated by a pH of 3-4 in the duodenum and by a pH of 1.5 in the stomach. Upon initiation of the reflex, the release of gastrin by G-cells in the antrum of the stomach is shut off. This in turn inhibits gastric motility and the secretion of gastric acid (HCl).
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.
Local hormones are a large group of signaling molecules that do not circulate within the blood. Local hormones are produced by nerve and gland cells and bind to either neighboring cells or the same type of cell that produced them. Local hormones are activated and inactivated quickly. They are released during physical work and exercise. They mainly control smooth and vascular muscle dilation. Strength of response is dependent upon the concentration of receptors of target cell and the amount of ligand.