INSL5
The gut hormone from the far end of the bowel: it makes mice eat, moves the colon, and in people has only ever been measured
Insulin-like peptide 5 (INSL5) is a two-chain hormone of the insulin and relaxin family, made by the same L cells of the colon and rectum that produce GLP-1 and PYY. Its receptor, RXFP4, sits mostly in the gut. In mice it raises food intake when energy is short and its engineered analogues speed the colon along; in people it has been measured in blood and tissue, rising after bile acid reaches the rectum and falling after weight-loss surgery. Nobody has been given it.
No established human dose Details ↓
Recommended Dosing
No established human dose
No study on this page gave INSL5 to a person. The human evidence is measurement and expression: the peptide and its receptor located in colon, rectum and tumour tissue, its chains read off human colonic samples by mass spectrometry, plasma and serum levels compared between groups of women with polycystic ovary syndrome, people before and after weight-loss surgery, patients with chronic diarrhoea and patients with nasopharyngeal carcinoma, and two studies that watched levels change after a bile acid enema or a glucose drink.
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What is it?
Insulin-like peptide 5 was not discovered by anyone looking for a gut hormone. In 1999 a group trawling gene databases for the arrangement of cysteines that marks insulin's B chain pulled out a new gene, named it INSL5, and found it active in human rectum, colon and uterus. Like insulin it is built as a single precursor of 135 amino acids and cut down to two chains, a B chain of 24 residues and an A chain of 21, held together by three disulfide bonds. The A chain begins with an unusual residue, a cyclised glutamine called pyroglutamate.
For six years nobody knew what it did, because nobody knew what it acted on. In 2005 it was paired with an orphan receptor then called GPCR142 and now RXFP4, which it switches on at low nanomolar concentrations. The selectivity is one-sided and useful: the closely related brain peptide relaxin-3 activates both RXFP3 and RXFP4, while INSL5 leaves RXFP3 alone. That makes it the family's gut-facing member, as INSL3 is its reproductive one.
Where it comes from is now well established. In the human large bowel it sits in enteroendocrine cells of the mucosa, more densely towards the rectum, and in the mouse the same cells are the L cells better known for GLP-1 and PYY. Work with colonic cultures showed that more than four fifths of secretory vesicles hold all three hormones, which are released together when the cell is stimulated. That is an awkward arrangement, because GLP-1 and PYY reduce appetite and this one increases it in mice.
The blood pattern deepens the puzzle. In mice levels rise with fasting and with sustained calorie restriction and fall with feeding, and injections make mice eat more, an effect that disappears without the receptor. Mice bred without the gene are mostly normal but secrete less insulin as they age, have smaller islets, and show changes in liver glucose production; their colonic gene activity turns out to depend on their gut bacteria, rising when the colon lining is short of energy. A pharmaceutical group then gave it and a long-acting version repeatedly to obese mice and saw no useful change in weight, intake or glucose control, which is a serious mark against it as a metabolic drug target.
Human evidence is entirely measurement and expression. Blood levels have been compared between groups: higher in three studies of women with polycystic ovary syndrome and unchanged in a fourth, lower after sleeve gastrectomy, raised in bile acid diarrhoea, and higher in nasopharyngeal carcinoma. Two experiments come closer to physiology: a bile acid enema raised plasma levels within minutes in healthy volunteers, and levels dipped early during a glucose tolerance test. The assays themselves have been a problem, which is why one group built a mass-spectrometry method after reporting that commercial immunoassays were unreliable, and it is a reason to treat the group comparisons cautiously.
The therapeutic interest has moved. Early papers framed the peptide around appetite and diabetes; the most recent review frames it around colonic movement and chronic constipation, because engineered analogues of it speed the passage of material through the mouse colon and a purpose-built antagonist slows it. Those analogues are separate molecules with their own entries in the literature, and the natural peptide has never been given to a person. Anything offered for sale under this name sits outside any regulated supply.
Mechanism of Action
INSL5 is released from L cells at the far end of the bowel and acts on RXFP4, a receptor found mostly in the gut wall. In mice that signalling raises food intake when energy is short and speeds colonic transit; in people the same signalling has only been inferred from measurements.
Appetite when energy is short
Mouse blood levels rise with fasting and calorie restriction and injections increase eating, an effect absent in mice without the receptor (PMID 25028498).
Gut bacteria and energy supply
Colonic gene activity is higher in germ-free and antibiotic-treated mice and falls when the colon lining gets more energy (PMID 27069866).
Insulin and GLP-1
In mouse cells and live mice it increased glucose-stimulated insulin release and glucose-dependent GLP-1 release, and mice without the gene secreted less insulin (PMIDs 25514935, 22822165).
Colonic movement
Bile acid reaching the human rectum raised plasma levels alongside an urge to defecate, and in mice RXFP4 agonists built from this peptide speed colonic propulsion (PMIDs 40701790, 31989750).
Immune signals
In mice the receptor is present across immune organs and injection shifted several cytokines; in a macrophage line the peptide lowered inflammatory cytokines (PMID 33519716).
Published Research
These are studies of INSL5 and its gene, read from their PubMed abstracts: the gene hunt that found it, the work that matched it to RXFP4 and made it synthetically, mouse studies of appetite, insulin, liver glucose and immune signals, human tissue maps and mass spectrometry, ten human studies that measured it in blood or tissue, a test on human sperm in a dish, and two reviews. No human study gave it to anyone; the engineered analogues that were given to animals are listed under References.
Found by searching gene databases for an insulin signature
The gene was turned up by scanning expressed-sequence-tag collections for the pattern of cysteines that marks the B chain of insulin. Human and mouse versions both encode a 135-amino-acid precursor, and across the A and B chain regions the human sequence is about half identical to shark relaxin and roughly a third identical to the Leydig cell peptide now called INSL3. Northern blots picked up human gene activity in rectum, colon and uterus, and in mice the colon carried by far the most, followed by the thymus.
Matched to its receptor, RXFP4
A receptor then known as GPCR142 had no known natural partner. Human INSL5 competed with radiolabelled relaxin-3 for it with nanomolar affinity, bound it directly in a saturation assay and switched it on at low nanomolar concentrations in two functional readouts. The selectivity ran one way: INSL5 did essentially nothing at the relaxin-3 receptor GPCR135 except act as a weak blocker at micromolar levels, and nothing at all at the two receptors for relaxin-2 and INSL3. That pairing, plus overlapping tissue activity, is why RXFP4 is now treated as its receptor.
Difficult to synthesise, active once assembled
Chemists set out to make the two-chain peptide so its biology could be studied, and found both chains stubbornly resistant to routine solid-phase methods; the B chain needed an unusually strong base during deprotection. After the three disulfide bonds were formed one at a time and the chains joined, the synthetic product folded much like relaxin-3 and blocked cAMP production in cells carrying human RXFP4 with similar strength, while leaving the relaxin-3 receptor untouched.
Also made in the mouse hypothalamus
Working in mice, this group found gene activity in the hypothalamus and stained cells in the paraventricular, supraoptic and nearby nuclei, with fibres reaching the median eminence and signal in both lobes of the pituitary. The stained neurons were the vasopressin-making ones rather than the oxytocin ones. Applied to cultured hypothalamic neurons, the peptide raised cytosolic calcium both by letting calcium in and by releasing it from internal stores, an effect blocked by drugs that interfere with those stores.
A marker of hormone-making cells in the human large bowel
Staining of human colon placed the peptide exclusively in enteroendocrine cells of the mucosa, while the receptor appeared on the ordinary absorptive cells around them, which suggests local signalling between neighbours rather than a distant hormone. Both peptide and receptor also showed up in human neuroendocrine tumour tissue. Mice lacking the gene still developed their normal complement of these cells, and two chemically induced models of colitis did not change their number during the acute phase.
Concentrated towards the rectum, and in rectal tumours
A second group reported the same restriction to colorectal hormone cells, with the density rising along the bowel towards the rectum, and noted that these cells carry little chromogranin A, the usual marker for the family. Every rectal neuroendocrine tumour they examined carried both the peptide and its receptor. Knockout mice had a normal distribution of chromogranin-positive cells, and adding the peptide to human colon cancer cell lines did not change how fast they grew.
Mice without the gene secrete less insulin
Mice bred without the gene were born in the expected numbers and grew to normal weight, but both sexes were less fertile: sperm moved poorly and the female cycle ran irregularly. With age their fasting glucose rose, and tolerance tests traced this to weaker insulin release rather than resistance to insulin. Their pancreatic islets were smaller and held fewer beta cells, and the receptor was detectable on islet cells, which led the authors to suspect a signal from gut to pancreas.
Released when food is short, and it makes mice eat
This study identified the peptide as a product of the colonic L cell, the same cell that makes GLP-1 and PYY. Injected into the abdominal cavity it increased what mice ate, and that increase disappeared in mice lacking the receptor, so the effect runs through RXFP4. Blood levels climbed with fasting and with prolonged calorie restriction and fell again with feeding, the opposite pattern to the appetite-suppressing hormones made in the same cell. The authors concluded that it drives appetite when energy is scarce.
A push on insulin and GLP-1 release in mouse cells
The receptor was present in a mouse insulinoma cell line, and the peptide increased glucose-stimulated insulin release both in those cells and in live mice. In a mouse L cell line that also carries the receptor, it increased glucose-dependent GLP-1 release. The authors read this as an indirect route to better glucose handling, through insulin and GLP-1, and suggested the pair as a target in type 2 diabetes. Their conclusion sits awkwardly beside the appetite findings, and later work did not settle it.
Gut bacteria set how much is made
Colonic gene activity was higher in germ-free mice and in mice given antibiotics than in normally colonised ones, and it fell again when germ-free mice were colonised or fed a high-fat diet, so the signal tracks how much energy reaches the colon lining. Mice lacking the gene ate normally and handled oral glucose normally, but tolerated injected glucose worse, responded better to insulin and produced less glucose in the liver. The authors proposed that it helps the liver make glucose when energy is short.
Its exact human chains read off by mass spectrometry
Because commercial immunoassays for the peptide had proved unreliable, this group built a mass-spectrometry method instead. Peptides pulled from purified mouse L cells and from human and mouse colon tissue gave the precise sequences of the A and B chains; the human chains matched what had been predicted from the gene, while the mouse product differed from the database entry. The method also measured the peptide in the fluid above human and mouse colon cultures, where it rose after a known L cell stimulus.
Packed into the same vesicles as GLP-1 and PYY
Colonic cultures from mice and from human tissue were used to ask how one cell can release an appetite-raising hormone alongside two appetite-lowering ones. The cells carried the same receptors for fatty acids, bile acids and angiotensin as other L cells, and agonists at those receptors triggered calcium signals and release. Across many stimuli the three hormones came out together, and more than four fifths of secretory vesicles held all three. The authors put the opposing blood patterns down to different stimuli reaching the near and far ends of the gut.
Which signals it sets off inside cells
In a human L cell line, the peptide switched on the ERK, AKT and S6 kinase pathways and suppressed cAMP without releasing calcium. Its effect on GLP-1 release depended on timing: added briefly it did nothing to carbachol- or insulin-driven release and modestly damped release driven by forskolin, while 18 hours of exposure raised baseline release and cancelled the acute damping. Two other cell lines with the receptor did not respond at all, and a mouse L cell line lacked the receptor.
A natural variant that works normally
A sequence change at position 27 of the B chain had been found in an Amish population and linked with a healthier metabolic picture, with the suggestion that the altered peptide might block its own receptor. The authors made the variant and tested it: at human RXFP4 it was as potent and as effective as the ordinary peptide, so receptor blockade cannot explain the association. They also reported chemical improvements that made the difficult B chain easier to build.
No metabolic benefit in obese mice
A pharmaceutical group set out to confirm the appetite effect before combining the peptide with better-established agents. They made it by two synthetic routes, one of them attached to a 20-kilodalton polyethylene glycol chain to slow clearance, and gave both repeatedly at high levels to normal and obese mice. Neither form produced a meaningful change in food intake, body weight or glucose control, and the authors concluded that the peptide has little part in either.
Signals that reach the immune system in mice
Database searches and mouse experiments were combined to ask whether the pair has an immune role. Gene activity showed up in the thymus as well as the colon and tracked a marker of thymocyte development, while the receptor appeared across immune organs and most strongly on dendritic cells of the spleen. Injected into the abdominal cavity of mice, the peptide raised blood GLP-1, GIP, glucagon and PYY and shifted several cytokines. In a macrophage line it slowed growth and lowered the inflammatory cytokines interleukin-1 beta, interleukin-6 and TNF-alpha.
Human sperm carry the receptor
Semen samples from men with normal results were incubated with the peptide at several concentrations and for several lengths of time. The receptor protein was found on the neck and midpiece of the sperm and its gene was detected there by nested PCR. Exposure lowered the amount of reactive oxygen species produced by sperm mitochondria, most clearly at an intermediate concentration after four hours, and total motility was better preserved than in untreated samples. This is human tissue in a dish, not treatment of a person.
Blood levels tracked sex hormones and body fat
Serum was measured in 76 lean and obese men and women, and again in 14 men before and after weight-loss surgery. In obese men the level fell as testosterone and blood fats rose and climbed with cortisol; in obese women the clearest relation was an inverse one with C-reactive protein. After surgery the men's levels dropped while their testosterone recovered. The study is cross-sectional apart from the surgical arm, and its correlations differ by sex and by weight, so it describes associations rather than a mechanism.
Higher in women with polycystic ovary syndrome
In 82 women with polycystic ovary syndrome and 82 controls matched for age and body mass index, serum levels were markedly higher in the syndrome group. Within both groups overweight women had higher levels than lean women, and among the women with the syndrome those with insulin resistance had more than those without. Levels moved with insulin resistance, body mass index, luteinising hormone and free androgen index, and the top third of levels carried the highest odds of having the syndrome.
Tracking with anti-Mullerian hormone
A case-control study of 117 women with polycystic ovary syndrome and 100 healthy women sorted everyone into quarters by serum level and found mean anti-Mullerian hormone rising steadily across them, from about 4.6 to about 9.5 ng/ml. The trend survived adjustment for age, body mass index, metabolic measures, oestradiol and testosterone. Anti-Mullerian hormone remained the better diagnostic test of the two, and the authors read the pairing as a sign of raised androgen production and absent ovulation.
Linked to insulin resistance
Serum from 101 women with polycystic ovary syndrome and 78 controls was measured by immunoassay. Levels were higher in the syndrome group and correlated moderately with three separate indices of insulin resistance. Women in the top third of levels were about twelve times as likely to have the syndrome as those in the bottom third after adjustment, and the association with the main insulin-resistance index held in multiple regression. As a cross-sectional study it cannot say which came first.
A prospective study that found no group difference
Forty-five women with newly diagnosed polycystic ovary syndrome and 35 age-matched controls were compared. Median serum levels did not differ between the groups, which runs against the three earlier reports. Inside the syndrome group the correlations ran in the opposite direction to those studies: levels fell as body mass index, insulin, insulin resistance, cholesterol, triglycerides, fat mass and free androgen index rose, and rose with sex hormone binding globulin. The authors concluded it has no diagnostic value here.
Falls after weight-loss surgery
Plasma was measured in people with severe obesity before and after sleeve gastrectomy. Before surgery levels rose with body mass index, fat mass and leptin; afterwards they were significantly lower. Human fat tissue produced none of the peptide at either gene or protein level, so the fall cannot be explained by losing fat tissue itself. Given the appetite effect seen in mice, the authors suggest the drop could contribute to the reduced appetite that follows such operations.
Bile acid in the rectum releases it in people
Using a new immunoassay, this group measured the peptide in stored samples from several studies: seven healthy volunteers given a rectal enema of taurocholic acid, ten given a mixed meal, and patients with bile acid diarrhoea or diarrhoea-predominant irritable bowel syndrome. The bile acid enema, but not a control enema, raised plasma levels promptly, and the rise tracked how soon and how strongly volunteers needed to defecate. A meal changed nothing in healthy people, whose levels stayed low. Levels were raised in bile acid diarrhoea and tracked stool consistency, and the 42 per cent of irritable bowel patients with raised levels responded better to ondansetron.
An early dip during a glucose tolerance test
This exploratory study followed plasma levels through an oral glucose tolerance test in people with severe obesity. Levels fell early, in step with the rise in glucose and insulin, which the authors take as a hint that nutrients arriving in the upper gut can influence a hormone made at the far end of the bowel. They are careful to say the design cannot show how that happens, and they frame the result as a reason for larger studies rather than a finding about treatment.
Raised in nasopharyngeal cancer tissue and plasma
In nasopharyngeal carcinoma the peptide was higher in tumour tissue and in patients' plasma than in comparison samples, and higher plasma levels went with worse outcomes; the authors propose it as a marker where the usual antibody test is negative. In cells, extra peptide increased growth, colony formation and invasion, while knocking down the receptor or blocking the peptide reduced them, and the peptide drove STAT5 activation and genes of glucose breakdown. Mouse tumour experiments pointed the same way.
Gene activity differs between the two inflammatory bowel diseases
Published expression data were screened for cytokine genes that move in opposite directions in ulcerative colitis and Crohn's disease, and three candidates, including this one, were taken forward for laboratory confirmation in patient tissue. Measured directly, the gene was less active in both diseases, following the direction the screen predicted. The authors offer the three genes as possible aids in telling the two conditions apart, and are explicit that more work on protein levels and gene regulation is needed.
A proposed role as a guard against energy shortage
This review gathers the scattered findings and argues they fit a hormone that reports energy availability and protects against shortage, rather than one with a single job. It draws together evidence that the pair dampens inflammatory cytokine production and may touch the stress axis, that it could signal through sensory fibres of the vagus nerve to the brain, and that much of its action may be local within the gut wall and immune cells. The authors are clear that no consensus exists.
The current view: a regulator of colonic movement
The most recent review describes the peptide as a product of L cells in the far end of the gut and its receptor as largely confined to the gastrointestinal tract, signalling through inhibitory G proteins. It summarises the structural work, the run of synthetic analogues built because the natural peptide is hard to make, and the evidence that this signalling helps control how the colon moves. Its stated therapeutic interest is chronic constipation rather than obesity or diabetes.
No Established Human Dose
No study on this page gave INSL5 to a person. The human evidence is measurement and expression: the peptide and its receptor located in colon, rectum and tumour tissue, its chains read off human colonic samples by mass spectrometry, plasma and serum levels compared between groups of women with polycystic ovary syndrome, people before and after weight-loss surgery, patients with chronic diarrhoea and patients with nasopharyngeal carcinoma, and two studies that watched levels change after a bile acid enema or a glucose drink. The only human material exposed to the peptide was semen in a dish. There is no INSL5 medicine and no amount to state for a person.
What this rests on: PMID 23128569, PMID 28857318, PMID 40701790, PMID 37297947, PMID 28986276.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, 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 INSL5 is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of INSL5 has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store INSL5, 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 INSL5 stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking INSL5. What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
Unknown: no cited half-life and no label or trial duration on this page says how long INSL5 lasts or how long it was given. Results reported in the studies are under Published Research.
Side effects, and when to stop or get help
From the Side Effects section: Injected into mice it increased food intake, an effect that required its receptor (PMID 25028498); In mice it raised blood GLP-1, GIP, glucagon and PYY and shifted several cytokines (PMID 33519716); Mice bred without the gene released less insulin with age, had smaller islets and were less fertile (PMID 22822165); Given repeatedly at high levels to obese mice, it changed neither weight nor glucose control, so even its animal effects are inconsistent (PMID 31348991); No study read gave it to a person, so its human safety is unknown. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping INSL5. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“INSL5 has never been given to a person, so it has no recorded human side effects”).
Interactions
Unknown: a PubMed search for human interaction studies of INSL5 (reviewed 2026-11-03) 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 INSL5 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 INSL5's expected mass, 5,044.8 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: an endogenous human gut hormone studied in animals and measured in people). 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
INSL5 has never been given to a person, so it has no recorded human side effects. These are the effects reported in animals and in cells.
Contraindications & Cautions
There is no INSL5 medicine. These cautions concern the peptide as a research chemical and the blood tests built around it.
Legal Status
INSL5 is an endogenous human hormone studied in animals and measured in people; it is not approved as a medicine anywhere in the sources read.
Frequently Asked Questions
?What is INSL5?
A two-chain hormone of the insulin and relaxin family, made by hormone-producing L cells in the colon and rectum. Its receptor, RXFP4, is found mostly in the gut wall.
?What does INSL5 do?
In mice it rises with fasting and makes them eat more, and signalling at its receptor speeds the colon along. In people it has only been measured, so its job here is inferred rather than shown.
?Is INSL5 the same as insulin?
No. It belongs to the same superfamily and shares the two-chain, disulfide-bonded architecture, but it is a different gene with a different receptor and it does not act like insulin. It is a closer relative of relaxin-3 and INSL3.
?Is INSL5 a weight-loss peptide?
No. If anything the mouse work points the other way, since injections increased food intake. A drug company that gave it and a long-acting version to obese mice found no useful effect on weight, intake or glucose control.
?Why do blood levels of INSL5 disagree between studies?
Most group comparisons rest on commercial immunoassays, and one group reported those assays unreliable and built a mass-spectrometry method instead. The four studies in polycystic ovary syndrome disagree even on the direction of some correlations.
?Can you take INSL5?
No. No study has given it to a person, there is no approved product, and no human dose exists. The analogues that have been given to animals are separate molecules.
References
- [other] UniProt Q9Y5Q6 (INSL5_HUMAN), B chain = residues 23-46, A chain = residues 115-135 with an N-terminal pyroglutamate, two interchain disulfide bonds and one within the A chain; read November 3, 2026. Formula and mass computed from the two chains with three disulfides. https://www.uniprot.org/uniprotkb/Q9Y5Q6/entry
- [pubmed] Conklin D, et al. "Identification of INSL5, a new member of the insulin superfamily." Genomics, 1999;60(1):50-6. PMID: 10458910.
- [pubmed] Liu C, et al. "INSL5 is a high affinity specific agonist for GPCR142 (GPR100)." J Biol Chem, 2005;280(1):292-300. PMID: 15525639.
- [pubmed] Akhter Hossain M, et al. "Synthesis, conformation, and activity of human insulin-like peptide 5 (INSL5)." Chembiochem, 2008;9(11):1816-22. PMID: 18576448.
- [pubmed] Dun SL, et al. "Insulin-like peptide 5: expression in the mouse brain and mobilization of calcium." Endocrinology, 2006;147(7):3243-8. PMID: 16601133.
- [pubmed] Thanasupawat T, et al. "INSL5 is a novel marker for human enteroendocrine cells of the large intestine and neuroendocrine tumours." Oncol Rep, 2013;29(1):149-54. PMID: 23128569.
- [pubmed] Mashima H, et al. "INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors." Biochem Biophys Res Commun, 2013;432(4):586-92. PMID: 23438439.
- [pubmed] Burnicka-Turek O, et al. "INSL5-deficient mice display an alteration in glucose homeostasis and an impaired fertility." Endocrinology, 2012;153(10):4655-65. PMID: 22822165.
- [pubmed] Grosse J, et al. "Insulin-like peptide 5 is an orexigenic gastrointestinal hormone." Proc Natl Acad Sci U S A, 2014;111(30):11133-8. PMID: 25028498.
- [pubmed] Luo X, et al. "The insulinotrophic effect of insulin-like peptide 5 in vitro and in vivo." Biochem J, 2015;466(3):467-73. PMID: 25514935.
- [pubmed] Lee YS, et al. "Insulin-like peptide 5 is a microbially regulated peptide that promotes hepatic glucose production." Mol Metab, 2016;5(4):263-270. PMID: 27069866.
- [pubmed] Kay RG, et al. "Liquid chromatography/mass spectrometry based detection and semi-quantitative analysis of INSL5 in human and murine tissues." Rapid Commun Mass Spectrom, 2017;31(23):1963-1973. PMID: 28857318.
- [pubmed] Billing LJ, et al. "Co-storage and release of insulin-like peptide-5, glucagon-like peptide-1 and peptideYY from murine and human colonic enteroendocrine cells." Mol Metab, 2018;16:65-75. PMID: 30104166.
- [pubmed] Ang SY, et al. "INSL5 activates multiple signalling pathways and regulates GLP-1 secretion in NCI-H716 cells." J Mol Endocrinol, 2018;60(3):213-224. PMID: 29535183.
- [pubmed] Zaykov AN, et al. "Synthesis and Characterization of the R27S Genetic Variant of Insulin-like Peptide 5." ChemMedChem, 2018;13(8):852-859. PMID: 29466617.
- [pubmed] Zaykov AN, et al. "Insulin-like peptide 5 fails to improve metabolism or body weight in obese mice." Peptides, 2019;120:170116. PMID: 31348991.
- [pubmed] Vahkal B, et al. "Immune System Effects of Insulin-Like Peptide 5 in a Mouse Model." Front Endocrinol (Lausanne), 2020;11:610672. PMID: 33519716.
- [pubmed] Yeganeh IS, et al. "Expression and localization of relaxin family peptide receptor 4 in human spermatozoa and impact of insulin-like peptide 5 on sperm functions." Reprod Biol, 2017;17(4):327-332. PMID: 28986276.
- [pubmed] Wagner IV, et al. "Insulin-Like Peptide 5 Interacts with Sex Hormones and Metabolic Parameters in a Gender and Adiposity Dependent Manner in Humans." Horm Metab Res, 2016;48(9):589-94. PMID: 27355242.
- [pubmed] Bicer M, et al. "Circulating insulin-like peptide 5 levels and its association with metabolic and hormonal parameters in women with polycystic ovary syndrome." J Endocrinol Invest, 2019;42(3):303-312. PMID: 29956214.
- [pubmed] Chen Y, et al. "Insulin-like peptide 5 (INSL5) positively correlates with anti-Müllerian hormone (AMH) in women with the polycystic ovary syndrome: a case-control study." J Ovarian Res, 2022;15(1):118. PMID: 36303231.
- [pubmed] Chen Y, et al. "Insulin-like peptide 5 is associated with insulin resistance in women with polycystic ovary syndrome." J Diabetes Complications, 2023;37(7):108493. PMID: 37207506.
- [pubmed] Cengiz D, et al. "Metabolic and Hormonal Profile of Insulin-Like Peptide 5 (INSL5) in Polycystic Ovary Syndrome: A Prospective Analysis." Horm Metab Res, 2025;57(7):416-422. PMID: 40592474.
- [pubmed] Di Vincenzo A, et al. "Body Weight Reduction by Bariatric Surgery Reduces the Plasma Levels of the Novel Orexigenic Gut Hormone Insulin-like Peptide 5 in Patients with Severe Obesity." J Clin Med, 2023;12(11). PMID: 37297947.
- [pubmed] Bannon CA, et al. "Insulin-like peptide 5 is released in response to bile acid in the rectum and is associated with diarrhoea severity in patients with bile acid diarrhoea." Gut, 2026;75(2):278-288. PMID: 40701790.
- [pubmed] Di Vincenzo A, et al. "Early variations in plasma insulin-like peptide 5 during the oral glucose tolerance test: an exploratory study to further support the role of the proximal intestine in the regulation of food intake in obesity." Endocrine, 2026;91(1):24. PMID: 41489703.
- [pubmed] Li SB, et al. "Autocrine INSL5 promotes tumor progression and glycolysis via activation of STAT5 signaling." EMBO Mol Med, 2020;12(9):e12050. PMID: 32657028.
- [pubmed] Skok DJ, et al. "Expression of Cytokine-Coding Genes BMP8B, LEFTY1 and INSL5 Could Distinguish between Ulcerative Colitis and Crohn's Disease." Genes (Basel), 2021;12(10). PMID: 34680872.
- [review] Hechter D, et al. "Reviewing the physiological roles of the novel hormone-receptor pair INSL5-RXFP4: a protective energy sensor?." J Mol Endocrinol, 2022;69(1):R45-R62. PMID: 35521762.
- [review] Wu H, et al. "Understanding insulin-like peptide 5 (INSL5) and relaxin family peptide receptor 4 (RXFP4): structure, signalling, and function." RSC Chem Biol, 2026;7(7):1221-1236. PMID: 42256349.
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Sources & Citations
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