Pancragen
Also known as: Lys-Glu-Asp-Trp, Lys-Glu-Asp-Trp-NH2, H-Lys-Glu-Asp-Trp-NH2, tetrapeptide pancragen, KEDW
Short synthetic/endogenous tetrapeptide; bioregulatory peptide
What it is
Pancragen (Lys-Glu-Asp-Trp-NH2) is a tetrapeptide that stimulates expression of transcription factors regulating differentiation of acinar (Pdx1, Ptf1a) and islet of Langerhans (Pdx1, Pax6, Pax4, Foxa2, NKx2.2) pancreatic cells in aging cell cultures. It also tissue-specifically stimulates expression of differentiation factors CXCL12 and Hoxa3 in pancreatic cells. In aged pancreatic cell cultures, it increases expression of MMP2, MMP9, serotonin, glycoprotein CD79alpha, antiapoptotic protein Mcl1, and proliferation markers PCNA and Ki67, while decreasing proapoptotic protein p53. In animal models of diabetes, it exhibits hypoglycemic, endothelioprotective, and homeostatic effects. In non-human primate studies, it normalized insulin and C-peptide dynamics in response to glucose, suggesting recovery of endocrine pancreatic function (PMID 25946840, PMID 28509500). In human clinical observation, it decreased fasting blood glucose, improved glucose tolerance test results, and reduced insulin resistance in elderly patients with type 2 diabetes. Its inducing effect on differentiation markers is reported to be more pronounced in aged cultures, proposed as a mechanism of geroprotective action.
Class: Short synthetic/endogenous tetrapeptide; bioregulatory peptide
What it's studied for
- Correction of insulin resistance and carbohydrate metabolism disorders in elderly individuals with type 2 diabetes mellitus Human observational
- In 33 elderly patients with type 2 DM, pancragen significantly decreased fasting blood glucose, improved glucose tolerance test results, and reduced plasma insulin and insulin resistance index. No changes were observed in the control group not receiving pancragen. Nocturnal melatonin was found to be reduced by 70% in D PMID 22448364 Korkushko OV et al. Bulletin of experimental biology and medicine (2011)
- Correction of age-related endocrine pancreatic dysfunction (impaired glucose tolerance) in non-human primates Animal studies only
- Pancragen (50 µg/animal/day, intramuscularly, 10 days) markedly increased glucose disappearance rate and normalized plasma insulin and C-peptide dynamics in old female rhesus monkeys. Partial recovery persisted 3 weeks after drug discontinuation. PMID 25946840 Goncharova ND et al. Advances in gerontology (2014)
- Pancragen (0.05 mg/animal/day, intramuscularly, 10 days) decreased basal blood glucose and normalized insulin and C-peptide levels in old female rhesus monkeys with impaired glucose tolerance, compared to glimepiride (4 mg/animal/day per os). Glimepiride produced a more expressed and delayed hypoglycemic effect and C-p PMID 28509500 Goncharova ND et al. Advances in gerontology (2015)
- Hypoglycemic and endothelioprotective effects in experimental streptozotocin-induced diabetes mellitus (rat model) Animal studies only
- Oral pancragen produced a pronounced hypoglycemic effect in Wistar rats with streptozotocin-induced diabetes. Intramuscular pancragen normalized adhesion of mesenteric capillary endothelium but did not modify capillary permeability. PMID 18642713 Khavinson VKh et al. Bulletin of experimental biology and medicine (2007)
- Biological activity of Lys-Glu-Asp-Trp-NH2 was evaluated in rats during ontogeny and in streptozotocin-induced diabetes (model of rapid experimental aging) by metabolic parameters characterizing apoptosis (further details limited in abstract). PMID 21246099 Khavinson VKh et al. Bulletin of experimental biology and medicine (2010)
- Stimulation of pancreatic cell differentiation and functional activity during aging (in vitro) In vitro only
- Pancragen stimulated expression of differentiation factors Pdx1, Ptf1a (acinar) and Pdx1, Pax6, Pax4, Foxa2, NKx2.2 (islet of Langerhans) in both young and aged human pancreatic cell cultures. Differentiation marker expression was reduced with aging. PMID 23486591 Khavinson VKh et al. Bulletin of experimental biology and medicine (2013)
- In aged human pancreatic cell cultures, the tetrapeptide H-Lys-Glu-Asp-Trp-NH2 increased expression of MMP2, MMP9, serotonin, CD79alpha, Mcl1, PCNA, and Ki67, and decreased p53 expression. PMID 23734516 Khavinson VKh et al. Advances in gerontology (2012)
- Pancragen (Lys-Glu-Asp-Trp) tissue-specifically stimulated expression of CXCL12 and Hoxa3 in human embryonic pancreatic cells; effect was more pronounced in aged (late-passage) cultures. PMID 22808515 Khavinson VKh et al. Bulletin of experimental biology and medicine (2012)
- Tissue-specific stimulation of reparative processes in pancreatic tissue explants during aging (organotypic culture) In vitro only
- Pancragen at 0.05 ng/mL showed a stimulating effect in organotypic pancreatic tissue cultures from both young (3-week-old) and aged (18-month-old) Wistar rats, compared to control explants. PMID 17152728 Zakutskiy AN et al. Advances in gerontology (2006)
Community-reported dosing
| Route | Dose | Frequency / Duration | Population / context | Source tier |
|---|---|---|---|---|
| Intramuscular injection | 50 µg/animal per day | 10 days | animal | Research PMID 25946840 |
| Intramuscular injection | 0.05 mg/animal per day | 10 days | animal | Research PMID 28509500 |
| In vitro (tissue culture) | 0.05 ng/mL | Not specified (organotypic culture experiment) | in_vitro | Research PMID 17152728 |
| Oral and intramuscular | Not explicitly stated (oral and intramuscular routes studied) | Not explicitly stated in abstract | animal | Research PMID 18642713 |
| Not explicitly stated in abstract | Not explicitly stated in abstract | Not explicitly stated in abstract | human | Research PMID 22448364 |
Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.
Safety signals
- In the comparative primate study, glimepiride produced a 'more expressed and delayed hypoglycemic effect' relative to pancragen, suggesting pancragen carried a lower hypoglycemic burden; no adverse events from pancragen were explicitly reported PMID 28509500
- Authors described pancragen as 'effective and safe' for correction of age-related endocrine pancreatic dysfunction in old primates, but no formal safety metrics or adverse event data were reported in the abstract PMID 28509500
Frequently asked
What is pancragen and what is it made of?
Pancragen is a synthetic tetrapeptide with the amino acid sequence Lys-Glu-Asp-Trp (also written as Lys-Glu-Asp-Trp-NH2). It is described as an endogenous bioregulatory peptide studied primarily for its effects on pancreatic cell differentiation and glucose metabolism (PMID 23486591, PMID 21246099).
What has pancragen been studied for?
Published research has investigated pancragen for: (1) stimulating pancreatic cell differentiation in aging human cell cultures, including acinar and islet (Langerhans) cells; (2) correcting insulin resistance and blood glucose levels in elderly humans with type 2 diabetes; (3) restoring endocrine pancreatic function in aged non-human primates (PMID 25946840, PMID 28509500); and (4) hypoglycemic and endothelioprotective effects in rat models of streptozotocin-induced diabetes. Most studies are small-scale and/or in animal models.
What dose of pancragen should I take?
I'm not a medical professional and can't recommend a protocol for you specifically. What research has shown: Animal studies used 50 µg/animal/day intramuscularly for 10 days in old rhesus monkeys (PMID 25946840, PMID 28509500). The one human observational study did not report dose or route details in the available abstract. No human pharmacokinetic or dose-finding studies were identified in the reviewed literature.
Can I combine pancragen with other peptides or medications for better blood sugar control?
I can't recommend combining compounds — that's a prescribing decision. Here's what has been studied individually: Pancragen has been compared to glimepiride (a sulfonylurea) in old rhesus monkeys; both reduced basal blood glucose, but glimepiride produced a more pronounced hypoglycemic effect. No combination protocols with other peptides or medications were described in the reviewed abstracts.
How is pancragen administered — can it be taken orally or does it need to be injected?
Both oral and intramuscular routes have been reported in animal studies. In a rat study, oral pancragen produced a pronounced hypoglycemic effect, while intramuscular pancragen normalized capillary endothelial adhesion. In non-human primate studies, intramuscular injection was used (PMID 25946840, PMID 28509500). The route used in the human observational study was not stated in the available abstract. No data on oral bioavailability or comparative effectiveness between routes in humans are available from the reviewed abstracts.
Is pancragen safe for humans?
The available literature does not include dedicated human safety or pharmacokinetic studies. One small human observational study reported benefits in elderly patients with type 2 diabetes but did not describe adverse events in the available abstract. In a primate study, authors described pancragen as 'effective and safe,' but no formal adverse event data were reported. I don't have reliable study data on comprehensive human safety. I won't guess — please consult a licensed provider or peer-reviewed literature directly.
Is pancragen approved by the FDA or any regulatory agency?
The reviewed abstracts do not state the regulatory status of pancragen in any jurisdiction, including the US FDA, Health Canada, or WADA. Pancragen was described as originating from the St. Petersburg Institute of Bioregulation and Gerontology, but regulatory approval status is not addressed in the available literature. Please consult a licensed healthcare provider or the relevant regulatory authority for current status.
How does pancragen work in the pancreas?
Based on in vitro studies, pancragen stimulates transcription factors that regulate differentiation of both acinar cells (Pdx1, Ptf1a) and islet of Langerhans cells (Pdx1, Pax6, Pax4, Foxa2, NKx2.2), effects that are reduced during cell aging. It also tissue-specifically stimulates expression of CXCL12 and Hoxa3 in pancreatic cells, with effects more pronounced in aged cultures. In aged human pancreatic cell cultures it increases antiapoptotic protein Mcl1 and proliferation markers (PCNA, Ki67) while decreasing proapoptotic p53. Authors propose that stimulation of pancreatic cell differentiation may underlie its observed anti-diabetic effects.
What conditions could disqualify me from using pancragen?
I can't suggest treatments for medical conditions or advise on individual contraindications. Please speak with a licensed healthcare provider. The reviewed abstracts do not report any specific contraindications for pancragen.
Where can I buy pancragen?
I don't recommend vendors or sources. Please consult a licensed provider.
References
- [1] PMID 22448364 — In 33 elderly patients with type 2 DM, pancragen significantly decreased fasting blood glucose, improved glucose tolerance test results, and reduced plasma insu
- [2] PMID 25946840 — Pancragen (50 µg/animal/day, intramuscularly, 10 days) markedly increased glucose disappearance rate and normalized plasma insulin and C-peptide dynamics in old
- [3] PMID 28509500 — Pancragen (0.05 mg/animal/day, intramuscularly, 10 days) decreased basal blood glucose and normalized insulin and C-peptide levels in old female rhesus monkeys
- [4] PMID 18642713 — Oral pancragen produced a pronounced hypoglycemic effect in Wistar rats with streptozotocin-induced diabetes. Intramuscular pancragen normalized adhesion of mes
- [5] PMID 21246099 — Biological activity of Lys-Glu-Asp-Trp-NH2 was evaluated in rats during ontogeny and in streptozotocin-induced diabetes (model of rapid experimental aging) by m
- [6] PMID 23486591 — Pancragen stimulated expression of differentiation factors Pdx1, Ptf1a (acinar) and Pdx1, Pax6, Pax4, Foxa2, NKx2.2 (islet of Langerhans) in both young and aged
- [7] PMID 23734516 — In aged human pancreatic cell cultures, the tetrapeptide H-Lys-Glu-Asp-Trp-NH2 increased expression of MMP2, MMP9, serotonin, CD79alpha, Mcl1, PCNA, and Ki67, a
- [8] PMID 22808515 — Pancragen (Lys-Glu-Asp-Trp) tissue-specifically stimulated expression of CXCL12 and Hoxa3 in human embryonic pancreatic cells; effect was more pronounced in age
- [9] PMID 17152728 — Pancragen at 0.05 ng/mL showed a stimulating effect in organotypic pancreatic tissue cultures from both young (3-week-old) and aged (18-month-old) Wistar rats,