Xenin Explained
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
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
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
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]
Further reading
- Feurle GE, Pfeiffer A, Schmidt T, Dominguez-Munoz E, Malfertheiner P, Hamscher G . Phase III of the migrating motor complex: associated with endogenous xenin plasma peaks and induced by exogenous xenin . Neurogastroenterol. Motil. . 13 . 3 . 237–46 . June 2001 . 11437986 . 10.1046/j.1365-2982.2001.00263.x. 30979914 .
- Feurle GE, Anlauf M, Hamscher G, Arnold R, Klöppel G, Weihe E . Xenin-immunoreactive cells and extractable xenin in neuroendocrine tumors of duodenal origin . Gastroenterology . 123 . 5 . 1616–26 . November 2002 . 12404236 . 10.1053/gast.2002.36590. free .
- Feurle GE, Ikonomu S, Partoulas G, Stoschus B, Hamscher G . 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 . March 2003 . 12609763 . 10.1016/s0167-0115(02)00281-1. 1818472 .
- Taylor AI, Irwin N, McKillop AM, Patterson S, Flatt PR, Gault VA . 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 . October 2010 . 20631047 . 10.1677/JOE-10-0085 . free .
- Leckstrom A, Kim ER, Wong D, Mizuno TM . Xenin, a gastrointestinal peptide, regulates feeding independent of the melanocortin signaling pathway . Diabetes . 58 . 1 . 87–94 . January 2009 . 18984739 . 2606897 . 10.2337/db08-0260 .
Notes and References
- Schiavo-Cardozo D, Lima MM, Pareja JC, Geloneze B . Appetite-regulating hormones from the upper gut: disrupted control of xenin and ghrelin in night workers . Clinical Endocrinology . 79 . 6 . 807–811 . December 2013 . 23199168 . 10.1111/cen.12114 . 24887534 .
- Mazella J, Béraud-Dufour S, Devader C, Massa F, Coppola T . Neurotensin and its receptors in the control of glucose homeostasis . Frontiers in Endocrinology . 3 . 143 . 2012 . 23230428 . 3515879 . 10.3389/fendo.2012.00143 . free .
- Feurle GE, Hamscher G, Kusiek R, Meyer HE, Metzger JW . 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 . November 1992 . 1429581 . 10.1016/S0021-9258(18)41670-5 . free .
- http://www.expasy.org/uniprot/P53621 UniProtKB/Swiss-Prot entry P53621 COPA_HUMAN
- Maryanovich AT, Kormilets DY, Polyanovsky AD . Xenin: the oldest after insulin? . Molecular Biology Reports . 45 . 2 . 143–150 . April 2018 . 29340900 . 10.1007/s11033-018-4147-2 . 254840756 .
- Craig SL, Gault VA, Irwin N . Emerging therapeutic potential for xenin and related peptides in obesity and diabetes . Diabetes/Metabolism Research and Reviews . 34 . 6 . e3006 . September 2018 . 29633491 . 10.1002/dmrr.3006 . 4756921 .
- Hussain MA, Akalestou E, Song WJ . Inter-organ communication and regulation of beta cell function . Diabetologia . 59 . 4 . 659–67 . April 2016 . 26791990 . 4801104 . 10.1007/s00125-015-3862-7 .