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Coatomer subunit alpha | |||||||
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Identifiers | |||||||
Symbol | COPA | ||||||
RefSeq | NP_001091868 | ||||||
UniProt | P53621 | ||||||
Other data | |||||||
Locus | Chr. 1 q23.2 | ||||||
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Xenin is a peptide hormone secreted from the chromogranin A-positive enteroendocrine cells called the K-cells in the mucous membrane of the duodenum and stomach of the upper gut. [1] [2] The peptide has been found in humans, dogs, pigs, rats, and rabbits.
In humans, xenin circulates in the blood plasma. [3] There is a relationship between peaks of xenin concentration in the plasma and the third phase of the Migrating Motor Complex. For example, infusion of synthetic xenin in fasting volunteers will cause phase III activity. After a meal (the 'postprandial state'), infusion of xenin increases both frequency and the percentage of aborally propagated contractions. In higher concentrations xenin stimulates exocrine pancreatic secretion and inhibits the gastrin-stimulated secretion of acid in dogs. Xenin is also produced in neuroendocrine tumors of the duodenal mucosa.
In vitro , xenin interacts with the neurotensin receptor 1.
Xenin is a 25-amino acid polypeptide. The amino acid sequence of xenin is identical to the N-terminal end of cytoplasmic coatomer subunit alpha, [4] from which xenin can be cleaved by aspartic proteases. Xenin is structurally related to the amphibian peptide xenopsin and to the neuropeptide neurotensin.
Surpassed by insulin, xenin reflects the second highest degree of homology traced along the evolutionary tree among the regulatory peptides, indicating its prominent structural conservatism. [5]
Proxenin is the precursor to xenin. It is a 35-amino acid polypeptide. Like xenin, its amino acid sequence exactly matches the N-terminus of coatomer subunit alpha. [4]
Xenin promotes beta-cell survival and xenin has been evaluated in animal models of obesity and diabetes where it has demonstrated an antidiabetic potential. [6] In humans, co-administration of xenin-25 and gastric inhibitory polypeptide (GIP) reduces postprandial glycemia by delaying gastric emptying. [7]
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.
Beta cells (β-cells) are specialized endocrine cells located within the pancreatic islets of Langerhans responsible for the production and release of insulin and amylin. Constituting ~50–70% of cells in human islets, beta cells play a vital role in maintaining blood glucose levels. Problems with beta cells can lead to disorders such as diabetes.
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.
Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises the concentration of glucose and fatty acids in the bloodstream and is considered to be the main catabolic hormone of the body. It is also used as a medication to treat a number of health conditions. Its effect is opposite to that of insulin, which lowers extracellular glucose. It is produced from proglucagon, encoded by the GCG gene.
Pancreatic polypeptide cells, or formerly as gamma cells (γ-cells), or F cells, are cells in the pancreatic islets of the pancreas. Their main role is to help synthesize and regulate the release of pancreatic polypeptide (PP), after which they have been named. The pancreatic islets, where PP cells reside, was discovered in 1869 by a German pathological anatomist and scientist, Paul Langerhans. PP cells help to make up the pancreas but are smallest in proportion to the other cells previously stated. The proportions can vary based on which animals are being studied, but in humans, PP cells make up less than 2% of the pancreatic islet cell population.
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 or stomach acid is the acidic component – hydrochloric acid of gastric juice, produced by parietal cells in the gastric glands of the stomach lining. With a pH of between one and three, gastric acid plays a key role in the 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 take part in the chemical process of digestion, which follows the mechanical process of digestion. Food consists of macromolecules of proteins, carbohydrates, and fats that need to be broken down chemically by digestive enzymes in the mouth, stomach, pancreas, and duodenum, before being able to be absorbed into the bloodstream. Initial breakdown is achieved by chewing (mastication) and the use of digestive enzymes of saliva. Once in the stomach further mechanical churning takes place mixing the food with secreted gastric acid. Digestive gastric enzymes take part in some of the chemical process needed for absorption. Most of the enzymatic activity, and hence absorption takes place in the duodenum.
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.
Gastric inhibitory polypeptide(GIP), also known as glucose-dependent insulinotropic polypeptide, 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.
Amylin, or islet amyloid polypeptide (IAPP), is a 37-residue peptide hormone. It is co-secreted with insulin from the pancreatic β-cells in the ratio of approximately 100:1 (insulin:amylin). Amylin plays a role in glycemic regulation by slowing gastric emptying and promoting satiety, thereby preventing post-prandial spikes in blood glucose levels.
Motilin is a 22-amino acid polypeptide hormone in the motilin family that, in humans, is encoded by the MLN gene.
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.
Peptide YY (PYY), also known as peptide tyrosine tyrosine, is a peptide that in humans is encoded by the PYY gene. Peptide YY is a short peptide released from cells in the ileum and colon in response to feeding. In the blood, gut, and other elements of periphery, PYY acts to reduce appetite; similarly, when injected directly into the central nervous system, PYY is also anorexigenic, i.e., it reduces appetite.
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.
The gastric inhibitory polypeptide receptor (GIP-R), also known as the glucose-dependent insulinotropic polypeptide receptor, is a protein that in humans is encoded by the GIPR gene.
Coatomer subunit alpha is a protein that in humans is encoded by the COPA gene.
Big gastrin (G-34) is a form of gastrin with 34 amino acids in its sequence. Big gastrin is a hormone produced by G cells and can be found inside of the stomach. G-34 promotes the secretion of gastric acid in dogs. In dogs, the half life of this peptide is between 14.7 and 16.8 minutes. In humans, an over production of this hormone by gastrinomas leads to Zollinger-Ellison Syndrome.