Xenin
 | This article includes a list of general references, but it lacks sufficient corresponding inline citations. (February 2008) |
| Coatomer subunit alpha | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | COPA | ||||||
| RefSeq | NP_001091868 | ||||||
| UniProt | P53621 | ||||||
| Other data | |||||||
| Locus | Chr. 1 q23.2 | ||||||
| |||||||
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.
Structure and sequence
[edit]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
[edit]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]
As a drug target
[edit]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]
References
[edit]- ^ Schiavo-Cardozo D, Lima MM, Pareja JC, Geloneze B (December 2013). "Appetite-regulating hormones from the upper gut: disrupted control of xenin and ghrelin in night workers". Clinical Endocrinology. 79 (6): 807–811. doi:10.1111/cen.12114. PMID 23199168. S2CID 24887534.
- ^ Mazella J, Béraud-Dufour S, Devader C, Massa F, Coppola T (2012). "Neurotensin and its receptors in the control of glucose homeostasis". Frontiers in Endocrinology. 3: 143. doi:10.3389/fendo.2012.00143. PMC 3515879. PMID 23230428.
- ^ Feurle GE, Hamscher G, Kusiek R, Meyer HE, Metzger JW (November 1992). "Identification of xenin, a xenopsin-related peptide, in the human gastric mucosa and its effect on exocrine pancreatic secretion". J. Biol. Chem. 267 (31): 22305–9. doi:10.1016/S0021-9258(18)41670-5. PMID 1429581.
- ^ a b UniProtKB/Swiss-Prot entry P53621 COPA_HUMAN
- ^ Maryanovich AT, Kormilets DY, Polyanovsky AD (April 2018). "Xenin: the oldest after insulin?". Molecular Biology Reports. 45 (2): 143–150. doi:10.1007/s11033-018-4147-2. PMID 29340900. S2CID 254840756.
- ^ Craig SL, Gault VA, Irwin N (September 2018). "Emerging therapeutic potential for xenin and related peptides in obesity and diabetes". Diabetes/Metabolism Research and Reviews. 34 (6): e3006. doi:10.1002/dmrr.3006. PMID 29633491. S2CID 4756921.
- ^ Hussain MA, Akalestou E, Song WJ (April 2016). "Inter-organ communication and regulation of beta cell function". Diabetologia. 59 (4): 659–67. doi:10.1007/s00125-015-3862-7. PMC 4801104. PMID 26791990.
Further reading
[edit]- Feurle GE, Pfeiffer A, Schmidt T, Dominguez-Munoz E, Malfertheiner P, Hamscher G (June 2001). "Phase III of the migrating motor complex: associated with endogenous xenin plasma peaks and induced by exogenous xenin". Neurogastroenterol. Motil. 13 (3): 237–46. doi:10.1046/j.1365-2982.2001.00263.x. PMID 11437986. S2CID 30979914.
- Feurle GE, Anlauf M, Hamscher G, Arnold R, Klöppel G, Weihe E (November 2002). "Xenin-immunoreactive cells and extractable xenin in neuroendocrine tumors of duodenal origin". Gastroenterology. 123 (5): 1616–26. doi:10.1053/gast.2002.36590. PMID 12404236.
- Feurle GE, Ikonomu S, Partoulas G, Stoschus B, Hamscher G (March 2003). "Xenin plasma concentrations during modified sham feeding and during meals of different composition demonstrated by radioimmunoassay and chromatography". Regul. Pept. 111 (1–3): 153–9. doi:10.1016/s0167-0115(02)00281-1. PMID 12609763. S2CID 1818472.
- Taylor AI, Irwin N, McKillop AM, Patterson S, Flatt PR, Gault VA (October 2010). "Evaluation of the degradation and metabolic effects of the gut peptide xenin on insulin secretion, glycaemic control and satiety". J. Endocrinol. 207 (1): 87–93. doi:10.1677/JOE-10-0085. PMID 20631047.
- Leckstrom A, Kim ER, Wong D, Mizuno TM (January 2009). "Xenin, a gastrointestinal peptide, regulates feeding independent of the melanocortin signaling pathway". Diabetes. 58 (1): 87–94. doi:10.2337/db08-0260. PMC 2606897. PMID 18984739.