Preptin
A beta-cell peptide that boosted insulin release and bone-cell growth in early experiments, and whose own activity is now in doubt
Preptin is a 34-amino-acid piece of the precursor of insulin-like growth factor 2. Discovered in 2001 inside the insulin granules of mouse beta cells, it leaves the pancreas together with insulin, and early experiments found that it raised glucose-driven insulin release and made bone-forming cells divide. Since then dozens of clinical studies have measured it in blood: it tends to run high in type 2 diabetes, gestational diabetes and polycystic ovary syndrome and low in osteoporosis. A careful 2024 study, however, found no activity at all for synthetic preptin, and it has never been given to a person.
No established human dose Details ↓
Recommended Dosing
No established human dose
Preptin has never been given to a person. Every human study on this page measured the preptin already circulating in blood, in diabetes, pregnancy, polycystic ovary syndrome, kidney failure, heart disease, osteoporosis and cancer, and one trial tracked how exercise changed it.
What is it?
Insulin is not the only thing a pancreatic beta cell releases. Its secretory granules also carry amylin, pancreastatin and, as a New Zealand group found in 2001, a 34-residue fragment of the precursor of insulin-like growth factor 2 (IGF2). They named it preptin. When glucose rose, cultured beta cells released preptin together with insulin; adding synthetic preptin increased insulin output in a way that levelled off at higher concentrations; and in an isolated rat pancreas, infusing preptin lifted the second phase of insulin release by about 30%, while antibodies that mopped it up cut both phases. The authors proposed that preptin amplifies the insulin response to glucose.
A second line of work followed in 2007, when the same group showed that preptin made rat and mouse bone-forming cells (osteoblasts) multiply at very low concentrations, protected them from dying when starved of serum, and increased bone area when injected into adult mice. Chinese groups later reported that it stimulated human osteoblasts in culture through ERK signalling and connective tissue growth factor. Because people with obesity and high insulin tend to have denser bones, preptin became one candidate for a messenger linking the pancreas to the skeleton.
Most of the human literature is measurement, not treatment. Studies have reported higher preptin in type 2 diabetes and impaired glucose tolerance, in gestational diabetes (in both mother and cord blood), in diabetic kidney disease and in people with calcified coronary arteries; a 2023 meta-analysis of eight studies found it higher in polycystic ovary syndrome, especially with insulin resistance. In the bone studies the direction flips: older men with osteoporosis and women after menopause had lower preptin, and in each case lower levels went with lower bone density. In people on haemodialysis, however, higher preptin went with lower spine density, and in prostate cancer it did not distinguish men with bone metastases.
Two cautions run through this work. The first is the assays: average levels in healthy controls range from about 400 ng/L in one study to over 2,000 ng/L in another, so numbers cannot be compared from paper to paper. The second is causation. Mice engineered to lack the preptin-coding part of the Igf2 gene grew normally; only females had a weaker insulin response to glucose, and on a high-fat diet the changes differed by sex. In 2024 a Czech team synthesised human, mouse and rat preptin and 16 variants and found no significant biological activity in any cell type they tested, suggesting that earlier effects may have come from IGF2 or its precursors rather than preptin itself.
Preptin has never been tested as a treatment in people, has no approval anywhere and has no human dose. It appears on this site because research catalogues list it and its name turns up beside metabolic and bone-health claims. What can honestly be said is that blood preptin tracks insulin-resistant states and, in some groups, bone density; whether preptin itself does anything in the body is an open question.
Mechanism of Action
Preptin is a cleavage product of the IGF2 precursor stored in beta-cell granules. The actions below come from cell and animal experiments, and a 2024 study that tested synthetic preptin found none of them.
Made from pro-IGF2
Cut from the E-peptide of the IGF2 precursor and packed into insulin granules, so it leaves the beta cell with insulin when glucose rises (PMID 11716772).
Insulin release
Raised glucose-stimulated insulin output in beta cells and a perfused pancreas, possibly through the IGF2 receptor and the PLC/PKC pathway (PMIDs 11716772, 22787110).
Bone-forming cells
Stimulated osteoblast division and survival through ERK signalling and connective tissue growth factor in rodent and human cell cultures (PMIDs 16912056, 19333718).
Contested
Synthetic preptin and 16 variants showed no significant activity in a 2024 comparison, and knockout mice have only mild, sex-specific changes (PMIDs 39264940, 36459047).
Published Research
Studies of preptin read from their PubMed abstracts: the discovery and the insulin and bone-cell experiments, the knockout mice, the 2024 study that found no activity, and the human studies that measured preptin in blood. No study has given preptin to a person, so every human card here is a measurement.
Discovery in beta-cell granules
Purifying peptides from the secretory granules of a mouse beta-cell line, the authors found a 34-residue fragment of the pro-IGF2 E-peptide that was released with insulin when glucose rose. Synthetic preptin increased insulin release from the cells in a saturable way; in a perfused rat pancreas it raised second-phase insulin release by 30%, and antibodies against it lowered both phases by 26-29%.
Bone-forming in cells and mice
Preptin made primary rat osteoblasts and osteoblast-like cell lines proliferate from about 10^-11 M, acting through the p42/p44 kinases of the MAPK/ERK pathway, and cut serum-starvation cell death by more than 20%. It did not change bone resorption in organ culture, and injections into adult mice increased bone area and mineralising surface.
How it may raise insulin release
In an insulin-secreting mouse cell line, preptin increased insulin output with concentration, to about the level reached with glibenclamide. Blocking phospholipase C or protein kinase C, or adding antibodies to the IGF2 receptor, reduced the effect, pointing to signalling through that receptor.
Human osteoblasts via ERK and CTGF
Preptin increased the growth and alkaline phosphatase activity of human osteoblasts and raised their output of connective tissue growth factor. Silencing that factor, or blocking ERK signalling, removed the effect, while p38 and JNK were not activated.
Compared with IGF-I, IGF-II and insulin
On human primary bone cells, IGF-I had a strong effect on osteoblast-like cells, IGF-II and preptin a modest one and insulin none. All four factors increased the formation and bone-resorbing activity of human osteoclasts, IGF-I most strongly.
No activity found in a broad test
The authors made human, mouse and rat preptin and 16 full-length and shortened variants and tested them side by side in several cell types. None showed significant biological activity, and the authors suggest that reported effects of preptin may reflect IGF2, its precursor forms or the experimental conditions.
Knockout mice: a female insulin effect
Mice lacking the preptin-coding part of Igf2 had normal body weight, body composition, beta-cell area and fasting glucose up to 47 weeks. Females, but not males, mounted a weaker insulin response to glucose. The authors concluded that preptin is not essential for glucose control but supports beta-cell function.
Knockout mice on a high-fat diet
On a low-fat diet, male knockout mice had lower blood glucose but thinner, less dense bone than normal mice. Females lacking preptin gained more fat and liver fat on a high-fat diet and lost the extra glucose-stimulated insulin release that normal females showed. Losing preptin did not protect against diet-induced metabolic harm or bone loss.
Higher in type 2 diabetes
Plasma preptin, measured by radioimmunoassay in 160 people, averaged 456 ng/L in type 2 diabetes against 416 in impaired glucose tolerance and 398 in matched controls, and was lower in men than women. In multiple regression only diastolic pressure, triglycerides, HDL cholesterol and free fatty acids were independently linked to it.
Tied to glucose tolerance, not PCOS
Among 126 women, those with impaired glucose tolerance had higher serum preptin than those with normal tolerance, whether or not they had polycystic ovary syndrome. Women with the syndrome had somewhat higher levels, but after adjustment preptin was linked to glucose tolerance and not to the syndrome itself.
PCOS meta-analysis
Pooling eight studies with 582 participants, serum preptin was higher in women with polycystic ovary syndrome than in controls (standardised mean difference 1.35), and the gap was larger in the subgroup with more insulin resistance (2.40). The authors call for further studies before using it as a marker.
Gestational diabetes: mother and cord
In 31 women with gestational diabetes and 31 matched pregnant controls, preptin was higher in both maternal serum and cord blood of the diabetes group. Maternal levels rose with age, fasting insulin and one-hour glucose, but neither maternal nor cord levels were linked to the baby's growth at birth.
Gestational diabetes: a diagnostic cutoff
Serum preptin was higher in 85 women with gestational diabetes than in 89 pregnant controls. A cutoff of 335.3 ng/L separated the groups with 97.6% sensitivity and 87.6% specificity in this single sample, which the authors present as promising for diagnosis.
Rises with diabetic kidney disease
In 234 people with type 2 diabetes and 78 healthy controls, serum preptin was higher in all diabetes groups and highest in those with the most albumin in their urine. It rose with body mass index, creatinine and the urine albumin ratio and fell with kidney filtration rate.
Linked to coronary calcification
Among 220 people with suspected heart disease scanned by CT, serum preptin was higher in those with any coronary calcium. It remained an independent predictor alongside age, sex, hypertension and beta-blocker use, and the top fifth of preptin levels carried 2.9 times the odds of a raised calcium score.
Lower in men with osteoporosis
In 133 older men, serum preptin was lowest in those with osteoporosis, intermediate with osteopenia and highest with normal bone mass. It rose with bone density and with every bone-formation marker measured, but showed no link with the bone-resorption marker TRACP-5b.
Falls after menopause
Among 60 women with low bone density and similar body weight, postmenopausal women had lower serum preptin than premenopausal women (about 2,102 against 2,667 ng/L). Preptin correlated weakly with estradiol and with hip and femoral-neck density, but not with lumbar spine density.
The opposite pattern on dialysis
In 73 people on long-term haemodialysis, preptin did not differ with diabetes status. It rose with years on dialysis, parathyroid hormone and osteocalcin, and higher preptin went with lower lumbar spine density, so the authors suggest it may reflect bone turnover in this group.
No link with prostate cancer bone spread
In 50 men newly diagnosed with prostate cancer, 23 with bone metastases on PSMA PET/CT, median serum preptin was about the same with and without metastases (388.6 against 399.6 ng/L), and it could not tell the groups apart (area under the curve 0.525).
Falls with exercise training
Obese men with metabolic syndrome were randomised to aerobic interval, resistance or combined training, or no exercise, three times a week for 12 weeks. Serum preptin and insulin fell in all three training groups, more with interval and combined training than with resistance training, while undercarboxylated osteocalcin and adiponectin rose.
After bariatric surgery
In 46 people followed for six months after sleeve gastrectomy or gastric banding, serum preptin rose, but the change fell just short of significance (p = 0.051), and individual changes went in both directions; irisin and adropin rose significantly.
Preptin and bone
This review gathers the cell and animal evidence that preptin favours osteoblasts and may influence osteocalcin, and the clinical studies reporting low preptin in osteoporosis. It describes preptin as a possible link between glucose metabolism and bone and raises it as a candidate bone-building therapy.
No Established Human Dose
Preptin has never been given to a person. Every human study on this page measured the preptin already circulating in blood, in diabetes, pregnancy, polycystic ovary syndrome, kidney failure, heart disease, osteoporosis and cancer, and one trial tracked how exercise changed it. The only studies that administered preptin used cell cultures, a perfused rat pancreas and mice, and a 2024 comparison of synthetic preptin found no activity. No human dose has been studied or can be stated.
What this rests on: PMID 18618352, PMID 31869474, PMID 16912056, PMID 39264940.
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 Preptin 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 Preptin 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 Preptin, 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 Preptin stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Preptin. 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 Preptin 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: No human safety data exist: every human study measured preptin in blood without giving it; In mice, losing preptin altered insulin release and bone structure in sex-specific ways, which shows only that the peptide may matter, not that giving it is safe (PMIDs 36459047, 37614298); High blood preptin travels with insulin resistance, diabetes and coronary calcification in observational studies; those links are associations, not effects of preptin (PMIDs 18618352, 29958889). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Preptin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Preptin has never been given to people, so no human side effects are known”).
Interactions
Unknown: a PubMed search for human interaction studies of Preptin (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 Preptin 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 Preptin's expected mass, 4,029.5 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: no approval and no human treatment trial 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
Preptin has never been given to people, so no human side effects are known.
Contraindications & Cautions
Preptin is not an approved medicine anywhere.
Legal Status
Preptin is a research peptide and a laboratory marker, not a medicine.
Frequently Asked Questions
?What is preptin?
A 34-amino-acid peptide cut from the precursor of IGF2. Pancreatic beta cells store it with insulin and release the two together when blood glucose rises.
?Does preptin build bone or raise insulin in people?
Nobody knows, because it has never been given to a person. Those effects were seen in cell cultures, a rat pancreas and mice, and a 2024 study that tested synthetic preptin carefully found no activity.
?Why is it measured in blood?
Researchers have looked for it as a marker. It tends to be higher in type 2 diabetes, gestational diabetes and polycystic ovary syndrome, and lower in osteoporosis, but no assay is used clinically and values differ widely between laboratories.
?Is high preptin bad for you?
High preptin travels with insulin resistance and some complications in observational studies. That does not show preptin causes harm; it may simply rise with insulin output.
?Is preptin the same as IGF-2?
No. It comes from the same precursor protein but from a different stretch of it, the E-peptide, and it is far shorter than mature IGF-2.
?Can preptin be bought or used?
It is not an approved medicine anywhere and has no human dose. Material sold under the name is a research chemical of unknown content.
References
- [pubmed] Buchanan CM, et al. "Preptin derived from proinsulin-like growth factor II (proIGF-II) is secreted from pancreatic islet beta-cells and enhances insulin secretion." Biochem J, 2001;360(Pt 2):431-9. PMID: 11716772.
- [pubmed] Cornish J, et al. "Preptin, another peptide product of the pancreatic beta-cell, is osteogenic in vitro and in vivo." Am J Physiol Endocrinol Metab, 2007;292(1):E117-22. PMID: 16912056.
- [pubmed] Cheng KC, et al. "Characterization of preptin-induced insulin secretion in pancreatic β-cells." J Endocrinol, 2012;215(1):43-9. PMID: 22787110.
- [pubmed] Liu YS, et al. "Connective tissue growth factor is a downstream mediator for preptin-induced proliferation and differentiation in human osteoblasts." Amino Acids, 2010;38(3):763-9. PMID: 19333718.
- [pubmed] Bosetti M, et al. "Effects and differentiation activity of IGF-I, IGF-II, insulin and preptin on human primary bone cells." Growth Factors, 2013;31(2):57-65. PMID: 23410103.
- [pubmed] Mrázková L, et al. "The final walk with preptin." PLoS One, 2024;19(9):e0309726. PMID: 39264940.
- [pubmed] Buckels EJ, et al. "Genetic ablation of the preptin-coding portion of Igf2 impairs pancreatic function in female mice." Am J Physiol Endocrinol Metab, 2022;323(6):E467-E479. PMID: 36459047.
- [pubmed] Buckels EJ, et al. "Preptin Deficiency Does Not Protect against High-Fat Diet-Induced Metabolic Dysfunction or Bone Loss in Mice." JBMR Plus, 2023;7(8):e10777. PMID: 37614298.
- [pubmed] Yang G, et al. "Circulating preptin levels in normal, impaired glucose tolerance, and type 2 diabetic subjects." Ann Med, 2009;41(1):52-6. PMID: 18618352.
- [pubmed] Bu Z, et al. "The relationship between polycystic ovary syndrome, glucose tolerance status and serum preptin level." Reprod Biol Endocrinol, 2012;10:10. PMID: 22309801.
- [pubmed] Sobhan Bahreiny S, et al. "Circulating serum preptin levels in women with polycystic ovary syndrome: A systematic review and meta-analysis." Int J Reprod Biomed, 2023;21(5):367-378. PMID: 37362092.
- [pubmed] Aslan M, et al. "Maternal serum and cord blood preptin levels in gestational diabetes mellitus." J Perinatol, 2011;31(5):350-5. PMID: 21164426.
- [pubmed] Kıraç UI, et al. "Maternal serum preptin levels in the pathogenesis and diagnosis of Gestational diabetes mellitus." J Med Biochem, 2023;42(2):311-317. PMID: 36987416.
- [pubmed] Wang R, et al. "Elevated serum preptin concentrations in patients with diabetic nephropathy." J Investig Med, 2019;67(7):1048-1052. PMID: 31182468.
- [pubmed] Li B, et al. "Preptin is a new predictor of coronary artery calcification." Clin Chim Acta, 2018;485:133-138. PMID: 29958889.
- [pubmed] Li N, et al. "Lower circulating preptin levels in male patients with osteoporosis are correlated with bone mineral density and bone formation." BMC Musculoskelet Disord, 2013;14:49. PMID: 23363476.
- [pubmed] Nazari Soltan Aahmad S, et al. "Investigation of the relation between bone mass density and serum preptin levels in pre- and postmenopausal women." J Bone Miner Metab, 2018;36(6):710-715. PMID: 29134283.
- [pubmed] Kałużna M, et al. "Is Preptin a New Bone Metabolism Parameter in Hemodialysis Patients?" Life (Basel), 2021;11(4). PMID: 33921361.
- [pubmed] Gülbağcı B, et al. "Association between serum preptin levels and bone metastasis in newly diagnosed prostate cancer: a prospective exploratory study." J Bone Oncol, 2026;60:100794. PMID: 42656999.
- [clinical-trial] Mohammad Rahimi GR, et al. "Effects of exercise training on serum preptin, undercarboxylated osteocalcin and high molecular weight adiponectin in adults with metabolic syndrome." Exp Physiol, 2020;105(3):449-459. PMID: 31869474.
- [pubmed] Glück M, et al. "Serum Irisin, Adropin, and Preptin in Obese Patients 6 Months After Bariatric Surgery." Obes Surg, 2019;29(10):3334-3341. PMID: 31209831.
- [review] Ungureanu MC, et al. "Preptin: A New Bone Metabolic Parameter?" Metabolites, 2023;13(9). PMID: 37755271.
- [other] UniProt P01344 (IGF2_HUMAN), peptide residues 93-126, preptin; read October 28, 2026. https://www.uniprot.org/uniprotkb/P01344/entry
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026. The sequence and its position in the IGF2 precursor come from UniProt; status from Drugs@FDA (openFDA) and the EMA medicines list. 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.