Xenin
A small peptide from the upper gut that slows stomach emptying when infused, studied in people since the 1990s but never made into a medicine
Xenin-25 was found in the human stomach lining in 1992 and is released into the blood after meals. Endocrine cells of the duodenum make it, many of them the same cells that make the incretin hormone GIP. Infused into volunteers it set off the gut's fasting contraction wave early and, at the higher of two rates tested, slowed stomach emptying and lowered blood sugar after a meal in people with and without type 2 diabetes. It has no known receptor of its own, is broken down quickly, and exists only as a research tool.
Used in human trials: 4 or 12 pmol/kg/min, Primed-constant infusion, Intravenous (Study: post-meal gastric emptying, adults with normal or impaired g...) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
Xenin was discovered while looking for a human counterpart to xenopsin, a frog-skin peptide. In 1992 a team purified a 25-residue peptide from human gastric mucosa that matched xenopsin in its final six amino acids and named it xenin-25. They also found it in human plasma, where it rose after a meal in ten volunteers. Its closest human relative is neurotensin, and some of its actions in the gut appear to run through the neurotensin receptor; no receptor of its own has been identified.
The peptide is an odd one in its origin. It is not cut from a dedicated hormone precursor but from the start of alpha-COP, a protein that helps form transport vesicles inside every cell. A 35-residue precursor called proxenin has also been described. In the human duodenum, xenin sits in a distinct type of endocrine cell that makes up a few percent of the gut's hormone-producing cells, and many of those cells also hold GIP, one of the two incretin hormones that boost insulin after eating. Tumours of duodenal origin often contain it, which led to a suggestion that it could help classify them.
Blood levels move with feeding. They rise when people merely see and chew food they do not swallow, rise with an ordinary meal, and climb further when stomach acid is suppressed with omeprazole. Researchers have measured it in children, in night-shift workers, in obese adults before and after gastric bypass, in polycystic ovary syndrome and in gestational diabetes. Those studies describe associations: lower levels in obese children, a weaker rise after a meal in night workers, higher levels in women with PCOS or gestational diabetes. None shows that xenin causes any of these states.
The more informative human studies infused synthetic xenin-25. A short infusion during fasting brought forward phase III of the migrating motor complex, the sweeping wave of contractions that clears the small intestine between meals. Longer infusions with a liquid meal, run by a group at Washington University in St. Louis, found that the higher rate tested slowed gastric emptying and lowered the glucose rise after the meal, reduced GLP-1 release, and caused diarrhoea in some volunteers. Xenin alone did not raise insulin secretion; given with GIP it briefly amplified insulin and glucagon release in people with normal or impaired glucose tolerance, but not in type 2 diabetes.
Much of the current interest in xenin comes from animal work. In mice it reduced food intake and restored the insulin response to GIP in an engineered strain, and laboratories have built longer-acting analogues, short fragments such as xenin-8 and hybrid peptides that combine a xenin fragment with other gut hormones. Those are separate molecules and are not covered here. A 2025 review concluded that xenin-based drugs remain an early idea whose value in people is unproven. No drug made from xenin has entered a registered treatment trial, and no regulator has approved one.
Mechanism of Action
Xenin-25 is released from duodenal endocrine cells after meals and seems to act mostly through nerves: on neurotensin receptors on gut and pancreatic nerve fibres, it slows the stomach, alters intestinal motility and changes the release of other gut hormones.
Neurotensin receptor on nerves
No xenin receptor is known. NTSR1, the neurotensin receptor it can use, sits on nerve fibres in human stomach muscle and pancreatic exocrine tissue, not on islet hormone cells.
Slower gastric emptying
At 12 pmol/kg/min, infused xenin-25 delayed emptying of a liquid meal and blunted the glucose rise in people with and without type 2 diabetes.
Gut motility
A short infusion triggered an early phase III of the fasting migrating motor complex, and after a meal increased propagated contractions.
Partner of GIP
Made in many of the same K cells as GIP; on its own it does not raise insulin, but with GIP it briefly amplified insulin and glucagon release in people without diabetes.
Published Research
These are studies of xenin-25 itself, read from their PubMed abstracts: its discovery and measurement in human blood and tissue, research infusions in volunteers and in people with impaired glucose tolerance, type 2 diabetes or gastric bypass, observational studies of blood levels, two mouse studies and three reviews. Analogues, fragments and hybrid peptides built from xenin are different molecules and are not carded here.
Xenin found in human stomach lining and blood
A 25-residue peptide was purified from human gastric mucosa and sequenced; it shares its last six residues with the frog peptide xenopsin. A radioimmunoassay in ten volunteers showed plasma xenin rising after a meal. Infused into dogs, synthetic xenin stimulated pancreatic secretion from 4 pmol/kg/min, with the largest effect at 64.
Xenin's family, precursor and gut actions
Reviews xenin as a member of the xenopsin and neurotensin family. It inhibits acid secretion stimulated by pentagastrin, triggers pancreatic secretion and alters small and large bowel motility, acting in the gut through the neurotensin receptor. A 35-residue precursor, proxenin, and the finding that xenin is the N-terminus of alpha-COP, from which pepsin or cathepsin E can release it, are described. Its physiological role was unknown.
The cells that make xenin
Antibodies to xenin stained a distinct endocrine cell type in the duodenal and jejunal lining of humans, rhesus monkeys and dogs, separate from serotonin, somatostatin, motilin, CCK, neurotensin and secretin cells. These cells were 4.6% of the hormone-producing (chromogranin A-positive) cells in the human duodenum, and in all three species xenin was found together with GIP in a subset of GIP cells.
Xenin and the fasting contraction wave
In 20 fasting volunteers, predefined peaks of plasma xenin were linked to phase III of the migrating motor complex. In a double-blind crossover in nine others, a 10-minute intravenous infusion of xenin at 4 pmol/kg/min set off an early phase III in every volunteer during fasting and, after a liquid meal, raised the frequency of contractions and the share that moved down the gut.
Seeing and chewing food releases xenin
In volunteers, plasma xenin rose during modified sham feeding (chewing food without swallowing it) when the meal arrived unseen from another room; when they had watched it being prepared, fasting levels were already high and rose no further. A normal meal also raised xenin. The authors concluded that cephalic, nerve-driven signals help release it.
Acid suppression raises blood xenin
Treatment with omeprazole increased fasting and post-meal plasma xenin along with gastrin and pepsinogens, while somatostatin did not change. Injected pentagastrin did not raise xenin, so the effect did not appear to come from gastrin; stomach pH seemed to regulate xenin levels.
Xenin in duodenal neuroendocrine tumours
Of 72 foregut and midgut neuroendocrine tumours, xenin-staining cells were found in 23 of 26 of duodenal origin, up to a fifth of their endocrine cells. Five duodenal gastrinomas held about 497 pmol of xenin per gram. Tumours from the lung, stomach, ileum and pancreas had none, so xenin marked duodenal origin.
Xenin with GIP briefly boosts insulin secretion
Fasting volunteers with normal or impaired glucose tolerance or type 2 diabetes received graded glucose infusions with vehicle, GIP, xenin-25 or both peptides on separate days. Xenin alone changed neither insulin secretion nor glucagon. Combined with GIP it transiently raised insulin secretion and glucagon in the two groups without diabetes, but not in type 2 diabetes.
Xenin raises pancreatic polypeptide through nerves
In the same graded-glucose design, xenin-25 increased pancreatic polypeptide, a marker of cholinergic nerve input to the islets, to a similar degree in people with normal glucose tolerance, impaired tolerance and type 2 diabetes, and GIP amplified that response. In human pancreas, the receptor NTSR1 was found on nerve fibres in the exocrine tissue rather than on islet hormone cells.
Xenin slows gastric emptying after a meal
Subjects with normal or impaired glucose tolerance or type 2 diabetes (10 to 14 per group) drank a liquid meal while receiving vehicle or xenin-25 at 4 or 12 pmol/kg/min from the meal to 300 minutes. Only the higher rate slowed gastric emptying and lowered post-meal glucose, similarly in all three groups. It also lowered GLP-1, not GIP, and left the insulin response to glucose unchanged; 90- and 300-minute infusions worked, 30-minute ones did not.
Gastric bypass blunts xenin's effects
Eight women who had had Roux-en-Y gastric bypass, without diabetes, received 0, 4 or 12 pmol/kg/min of xenin-25 with liquid meals. Xenin raised pancreatic polypeptide and neuropeptide Y as it did in non-surgical controls, but its ability to suppress GLP-1 and to cause diarrhoea was much weaker after bypass, and it had no significant effect on glucose, insulin secretion or glucagon.
Atropine does not block xenin's islet effects in people
Fasted adults with impaired glucose tolerance had eight graded glucose infusions with albumin, xenin-25, GIP or both, each with and without atropine. Atropine abolished the pancreatic polypeptide rise but did not change insulin secretion or glucagon, so the cholinergic route that carries xenin's effect on insulin in mice did not carry it in humans.
Xenin in spinal fluid falls with weight loss
In 13 obese patients studied before and about eight months after gastric bypass, blood xenin was higher than in lean subjects and fell after surgery. Cerebrospinal fluid xenin was about a tenth of the blood level, was higher in obesity and returned to normal after weight loss, tracking blood levels throughout.
Night workers show a blunted xenin rise
In 24 overweight women, night-shift workers had a much smaller rise in xenin after a test meal than day workers of similar BMI, along with weaker post-meal suppression of ghrelin, more body fat, poorer sleep and lower insulin sensitivity. The study was cross-sectional and could not show cause.
Plasma xenin in children
Fasting xenin averaged 371 pg/ml in ten healthy children and was similar in 53 children with inflammatory bowel disease, rising during treatment and remission. Twenty-six obese children had markedly lower levels, about 198 pg/ml, and an oral glucose load did not change them.
Higher xenin in polycystic ovary syndrome
In a case-control study of 31 women with PCOS and 30 controls, median serum xenin-25 was 45.5 pg/mL against 9.85 pg/mL. Xenin was independently associated with PCOS in a regression model, and a cut-off of 32.6 pg/mL identified it with 61% sensitivity and 87% specificity.
Higher xenin in gestational diabetes
Among 80 pregnant women at 24 to 28 weeks, the 40 with gestational diabetes had higher serum xenin-25 both fasting and two hours after a 75 g glucose drink than the 40 with normal glucose tolerance, despite similar age, BMI, fasting glucose and insulin.
Xenin, stress and mood in severe obesity
In 160 inpatients with obesity (mean BMI 47), plasma xenin and neurotensin were closely correlated. In women only, both peptides correlated weakly with perceived stress, anxiety, depressive symptoms and eating-disorder scores; no such link appeared in men.
Xenin curbs feeding in mice by its own route
Xenin given into the brain or the abdomen reduced food intake after fasting in a dose-dependent way and activated hypothalamic neurons. It still worked in leptin-deficient and agouti mice, and a melanocortin-receptor blocker did not stop it, so its appetite effect did not depend on the leptin or melanocortin systems.
Xenin restores the GIP insulin response in mice
In mice engineered to lack GIP-producing cells, which respond poorly to GIP as people with type 2 diabetes do, pharmacological doses of xenin-25 restored GIP-driven insulin release and lowered blood sugar; xenin alone did nothing. Atropine blocked the effect and isolated islets did not respond, pointing to a cholinergic nerve relay rather than a direct action on beta cells.
Xenin and related peptides in obesity and diabetes
Reviews xenin-25 as a peptide co-secreted with GIP from K cells, with no specific receptor known and some actions through the neurotensin receptor. It covers its effects on gut transit, satiety, insulin and glucagon secretion and beta-cell survival, and work in animal models on analogues, the fragment xenin-8 and hybrid peptides.
Xenin-derived peptides: where they stand
Describes native xenin as rapidly degraded with limited bioavailability, and engineered analogues that last hours rather than minutes in rodents. The authors call the human data a single pilot study awaiting independent confirmation and conclude that xenin-based treatments remain early-stage, with efficacy and safety in people unestablished.
Dosing Data
Xenin is not a medicine anywhere. These are the research infusion rates stated in the abstracts of published human studies; each was a single supervised study day, not a treatment course.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Xenin is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
No worked example: none of the doses on this page is a fixed amount in mg or mcg injected under the skin or into a muscle (the routes given are: intravenous). There is no home-mixing step to show. The reconstitution calculator does the arithmetic for any vial.
Source: the route and amount of each dose row in Dosing Data below.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Xenin, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Xenin stays intact once mixed.
How it is taken
As it was given in human studies: Intravenous (Primed-constant infusion; Study: post-meal gastric emptying, adults with normal or impaired glucose tolerance or type 2 diabetes).
For injection technique, sites and needle disposal, see the mixing guide.
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: not established by a measurement cited on this entry.
How long the doses were given: Study: post-meal gastric emptying, adults with normal or impaired glucose tolerance or type 2 diabetes: From the meal until 300 minutes (some 30- and 90-minute runs); Study: women after Roux-en-Y gastric bypass: One study day per rate; Study: healthy volunteers, fasting and post-meal gut motility: 10 minutes.
When effects appear: unknown; no source on this page gives a time to effect for Xenin. Results reported in the studies are under Published Research.
Source: Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Diarrhoea during xenin-25 infusion in healthy volunteers with normal glucose tolerance, much less so after gastric bypass (PMID 27288245); Slower stomach emptying and lower GLP-1 after a meal at the higher infusion rate (PMID 24356886); No safety data beyond single infusions lasting minutes to hours. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Xenin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the short infusion studies above, which reported little on safety”).
Interactions
Unknown: a PubMed search for human interaction studies of Xenin (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Xenin products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Xenin's expected mass, 2,971.6 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not a medicine anywhere in the sources read). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the short infusion studies above, which reported little on safety.
Contraindications & Cautions
No product label exists. These cautions follow from the evidence.
Legal Status
Xenin is a research peptide; it is not approved as a medicine anywhere in the sources read.
Frequently Asked Questions
?What is xenin?
A 25-amino-acid peptide made by endocrine cells in the upper small intestine and released into the blood after meals. It belongs to the same family as neurotensin.
?Does xenin lower blood sugar?
In one infusion study, the higher rate tested lowered the glucose rise after a liquid meal, mainly by slowing stomach emptying. It did not increase insulin secretion on its own.
?How is xenin related to GIP?
Many of the duodenal cells that make GIP also make xenin. Given with GIP, xenin briefly amplified insulin release in people without diabetes but not in type 2 diabetes.
?Where does xenin come from?
It is the first 25 residues of alpha-COP, a protein that helps build transport vesicles inside cells, and digestive enzymes such as pepsin can release it.
?Is xenin a weight-loss drug?
No. It reduced food intake in mice, and analogues are being studied in animals, but no xenin drug has been tested as a treatment in people.
?What side effects did volunteers have?
The abstracts mention diarrhoea during infusion in volunteers without bariatric surgery. The studies were single infusions and say little else about safety.
References
- [pubmed] Feurle GE, et al. "Identification of xenin, a xenopsin-related peptide, in the human gastric mucosa and its effect on exocrine pancreatic secretion." J Biol Chem, 1992;267(31):22305-9. PMID: 1429581.
- [review] Feurle GE. "Xenin--a review." Peptides, 1998;19(3):609-15. PMID: 9533652.
- [clinical-trial] Anlauf M, et al. "Localization of xenin-immunoreactive cells in the duodenal mucosa of humans and various mammals." J Histochem Cytochem, 2000;48(12):1617-26. PMID: 11101630.
- [clinical-trial] Feurle GE, et al. "Phase III of the migrating motor complex: associated with endogenous xenin plasma peaks and induced by exogenous xenin." Neurogastroenterol Motil, 2001;13(3):237-46. PMID: 11437986.
- [clinical-trial] Feurle GE, et al. "Xenin plasma concentrations during modified sham feeding and during meals of different composition demonstrated by radioimmunoassay and chromatography." Regul Pept, 2003;111(1-3):153-9. PMID: 12609763.
- [clinical-trial] Stoschus B, et al. "Effect of omeprazole treatment on plasma concentrations of the gastric peptides, xenin, gastrin and somatostatin, and of pepsinogen." J Pept Res, 1998;52(1):27-33. PMID: 9716248.
- [clinical-trial] Feurle GE, et al. "Xenin-immunoreactive cells and extractable xenin in neuroendocrine tumors of duodenal origin." Gastroenterology, 2002;123(5):1616-26. PMID: 12404236.
- [clinical-trial] Wice BM, et al. "Xenin-25 amplifies GIP-mediated insulin secretion in humans with normal and impaired glucose tolerance but not type 2 diabetes." Diabetes, 2012;61(7):1793-800. PMID: 22522617.
- [clinical-trial] Chowdhury S, et al. "The combination of GIP plus xenin-25 indirectly increases pancreatic polypeptide release in humans with and without type 2 diabetes mellitus." Regul Pept, 2013;187:42-50. PMID: 24183983.
- [clinical-trial] Chowdhury S, et al. "Xenin-25 delays gastric emptying and reduces postprandial glucose levels in humans with and without type 2 diabetes." Am J Physiol Gastrointest Liver Physiol, 2014;306(4):G301-9. PMID: 24356886.
- [clinical-trial] Sterl K, et al. "Metabolic responses to xenin-25 are altered in humans with Roux-en-Y gastric bypass surgery." Peptides, 2016;82:76-84. PMID: 27288245.
- [clinical-trial] Wang S, et al. "Cholinergic signaling mediates the effects of xenin-25 on secretion of pancreatic polypeptide but not insulin or glucagon in humans with impaired glucose tolerance." PLoS One, 2018;13(2):e0192441. PMID: 29466430.
- [clinical-trial] van de Sande-Lee S, et al. "Cerebrospinal fluid xenin levels during body mass reduction: no evidence for obesity-associated defective transport across the blood-brain barrier." Int J Obes (Lond), 2013;37(3):416-9. PMID: 22546776.
- [clinical-trial] Schiavo-Cardozo D, et al. "Appetite-regulating hormones from the upper gut: disrupted control of xenin and ghrelin in night workers." Clin Endocrinol (Oxf), 2013;79(6):807-11. PMID: 23199168.
- [clinical-trial] Mrózek B, et al. "Plasma xenin concentrations in children." Pediatr Endocrinol Diabetes Metab, 2012;18(1):5-8. PMID: 22525684.
- [clinical-trial] Guclu YA, et al. "The relationship between elevated serum xenin and insulin resistance in women with polycystic ovary syndrome: a case-control study." Gynecol Endocrinol, 2019;35(11):960-964. PMID: 31010340.
- [clinical-trial] Kucukbas GN, et al. "Maternal serum xenin-25 levels in gestational diabetes mellitus." Eur Rev Med Pharmacol Sci, 2023;27(20):9902-9907. PMID: 37916358.
- [clinical-trial] Wölk E, et al. "Neurotensin and Xenin Show Positive Correlations With Perceived Stress, Anxiety, Depressiveness and Eating Disorder Symptoms in Female Obese Patients." Front Behav Neurosci, 2021;15:629729. PMID: 33664656.
- [pubmed] Leckstrom A, et al. "Xenin, a gastrointestinal peptide, regulates feeding independent of the melanocortin signaling pathway." Diabetes, 2009;58(1):87-94. PMID: 18984739.
- [pubmed] Wice BM, et al. "Xenin-25 potentiates glucose-dependent insulinotropic polypeptide action via a novel cholinergic relay mechanism." J Biol Chem, 2010;285(26):19842-53. PMID: 20421298.
- [review] Craig SL, et al. "Emerging therapeutic potential for xenin and related peptides in obesity and diabetes." Diabetes Metab Res Rev, 2018;34(6):e3006. PMID: 29633491.
- [review] Gong B, et al. "Xenin-Derived Peptides: Multifaceted Regulators and Therapeutic Innovations in Metabolic Diseases." Drug Des Devel Ther, 2025;19:11799-11815. PMID: 41479596.
- [other] UniProt P53621: COPA_HUMAN, coatomer subunit alpha; peptide 1-25 is xenin (MLTKFETKSARVKGLSFHPKRPWIL) and peptide 1-35 is proxenin. Read October 28, 2026. https://www.uniprot.org/uniprotkb/P53621/entry
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026; a PubMed search for xenin in titles and abstracts returned 94 records, 46 of them naming human subjects or patients. The sequence is UniProt's. Regulatory status comes from Drugs@FDA (openFDA) and the EMA medicines list, read October 28, 2026. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.