Key Takeaways
- •IGF-1 is a 70-amino-acid peptide hormone structurally similar to insulin, primarily produced in the liver in response to growth hormone stimulation.
- •Its primary mechanism involves activation of the IGF-1 receptor (IGF-1R), a tyrosine kinase receptor that initiates downstream signaling through the PI3K/Akt and MAPK/ERK pathways.
- •Preclinical work has examined IGF-1R signalling in myoblast, neuronal and fibroblast cell systems and in rodent models, and most of that evidence remains at the in vitro or rodent stage.
- •As of July 2026, no registered human clinical trials were identified for IGF-1 as a research peptide for the applications discussed in this article.
- •IGF-1 is sold for laboratory research purposes only and is not approved by regulatory agencies for human consumption or therapeutic use.
Summary
IGF-1 is a 70 amino acid peptide hormone. It is the downstream mediator of the growth hormone axis: GH acts on the liver, the liver makes IGF-1, and IGF-1 is the molecule that reaches the IGF-1 receptor. Its structure is close enough to insulin's that the two cross-react weakly at each other's receptors.
It signals through IGF-1R, a receptor tyrosine kinase, which activates the PI3K/Akt and MAPK/ERK pathways. That part is textbook: the receptor is crystallised, the pathways are reproduced across many cell lines, and none of it is in dispute. What is far less settled is everything that has been reported in whole animals, where the work is small, mostly rodent, and thinly replicated.
One caution. IGF-1 circulates bound to six binding proteins, so a total IGF-1 measurement and a free IGF-1 measurement are different numbers. It is supplied for laboratory research only.
Evidence Quality Summary
| Evidence Area | Strength | Notes |
|---|---|---|
| IGF-1 structure and receptor binding | Strong | Well-characterized biochemically; crystal structures available |
| IGF-1 signaling pathways (PI3K/Akt, MAPK) | Strong | Extensively replicated in multiple cell lines and tissues |
| Myoblast signalling (in vitro/rodent) | Low to moderate | Reproduced in cell culture; limited replication in larger models |
| Neuronal cell signalling (in vitro/rodent) | Low | Preliminary evidence; few independent replications |
| Cancer biology association | Low to moderate | Evidence is largely correlational |
| Human clinical trials for research peptide applications | Very low | No registered trials identified for non-therapeutic research use |
Quick Answers
| Question | Current Evidence |
|---|---|
| Human trials conducted? | As of July 2026, no registered human clinical trials were identified for the research applications discussed. |
| Main mechanism? | Activation of IGF-1R tyrosine kinase, leading to PI3K/Akt and MAPK/ERK signaling cascades. |
| Evidence type? | Predominantly in vitro (cell culture) and in vivo (rodent models). |
| Toxicology established? | No; no toxicological profile has been established for the research material. |
| Approved for human use? | No; not approved for human consumption by FDA, EMA, or other regulatory bodies. |
What Is IGF-1?
Insulin-like growth factor 1 (IGF-1), also known as somatomedin C, is a 70-amino-acid single-chain polypeptide hormone with a molecular weight of approximately 7.6 kDa. Its full chemical name is insulin-like growth factor I (human), and its molecular formula is C₃₃₀H₅₁₂N₉₄O₁₀₁S₇ (as per PubChem CID 126352). IGF-1 shares approximately 50% amino acid sequence homology with proinsulin, which underlies its ability to bind to both the IGF-1 receptor (IGF-1R) and, with lower affinity, the insulin receptor.
Endogenously, IGF-1 is primarily synthesized in the liver under the regulation of growth hormone (GH) and is the principal downstream mediator of GH receptor signalling. It circulates bound to six IGF-binding proteins (IGFBPs), which modulate its free fraction and half-life. In research contexts, recombinant human IGF-1 (rhIGF-1) is commonly used to study cell proliferation, differentiation and receptor signalling in vitro and in animal models.
Proposed Mechanism of Action
IGF-1 acts primarily through binding to the IGF-1 receptor (IGF-1R), a transmembrane tyrosine kinase receptor with high structural homology to the insulin receptor. Upon ligand binding, IGF-1R undergoes autophosphorylation, which has been reported to recruit adaptor proteins such as insulin receptor substrate (IRS) and Shc. This initiates two major downstream signaling cascades:
- PI3K/Akt pathway: Activation of phosphatidylinositol 3-kinase (PI3K) leads to generation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3), which activates Akt (protein kinase B). Akt phosphorylates targets such as mTOR and FoxO transcription factors, and in cell culture this branch is associated with suppression of apoptosis and increased protein synthesis.
- MAPK/ERK pathway: Recruitment of Shc and Grb2 leads to activation of Ras, Raf, MEK, and extracellular signal-regulated kinases (ERK1/2). This pathway has been reported to regulate cell proliferation and differentiation.
Research in this area suggests that IGF-1 signaling is tightly regulated by IGFBPs, which can either enhance or inhibit IGF-1 binding to IGF-1R depending on the cellular context.
Preclinical Research Findings
Preclinical research on IGF-1 has primarily been conducted in vitro (cell culture) and in vivo (rodent models). The following summarizes the main areas of investigation by cell system:
Myoblast cell systems: In vitro, IGF-1 has been reported to stimulate proliferation and differentiation of myoblasts (muscle precursor cells) via PI3K/Akt activation. Rodent work has used local gene transfer to overexpress IGF-1 in skeletal muscle tissue, and the translational relevance of those models remains unclear.
Neuronal cell systems: In vitro studies using neuronal cell cultures have reported that IGF-1 reduces apoptosis induced by oxidative stress or serum deprivation, an effect attributed to Akt signalling. Rodent studies in this area exist but are few, and independent replication is limited.
IGF-1R signalling in model organisms: Reduced signalling through the insulin/IGF-1 receptor pathway has been studied genetically in nematodes and mice, where the pathway is conserved. IGF-1 has also been reported to promote cellular proliferation in certain contexts, which is why the same pathway is studied in cancer biology.
Insulin receptor cross-talk: In vitro studies have shown that IGF-1 can stimulate glucose uptake in adipocytes and myocytes in culture, which reflects its partial activity at the insulin receptor and the overlap of downstream IRS signalling. Rodent studies of this cross-talk have produced inconsistent findings.
Evidence Limitations
The evidence base for IGF-1 in research peptide applications has several important limitations:
- Limited replication: Many of the neuronal and myoblast studies have been conducted by single research groups with limited independent replication. This reduces confidence in the generalizability of results.
- Lack of human clinical trials: As of July 2026, no registered human clinical trials were identified on ClinicalTrials.gov for IGF-1 as a research peptide for the applications discussed in this article. Existing clinical trials for IGF-1 concern licensed recombinant products under regulatory review and have not addressed the preclinical research applications described here.
- Species differences: Rodent and human IGF-1 systems differ in binding protein profiles and receptor distribution, which may limit the translational relevance of rodent findings.
Handling and Interpretation Considerations
IGF-1 is a potent mitogen in cell culture, and that activity has consequences for how experiments are designed and read:
- Mitogenic activity as a confounder: IGF-1 stimulates proliferation in many cell types, so an assay that reads cell number or metabolic activity will register that effect regardless of the pathway under study. Matched vehicle controls and serum-free conditions matter.
- Insulin receptor cross-reactivity: Because of its structural similarity to insulin, IGF-1 has measurable activity at the insulin receptor. Assays intended to isolate IGF-1R signalling need receptor-selective controls or IGF-1R blockade to attribute a readout.
- Limited toxicology data: Comprehensive toxicological studies for IGF-1 as a research material are lacking, and no toxicological profile has been established for it.
- Research-only status: IGF-1 is not approved for human consumption by the FDA, EMA, or any other regulatory body. It is intended exclusively for laboratory research purposes.
Current Research Status
Current research on IGF-1 continues to explore its mechanisms, with several active areas:
- Biomaterials and delivery: Researchers are investigating IGF-1 release from hydrogels and nanoparticles, characterising release kinetics and retained bioactivity in preclinical models.
- Neurodegenerative disease models: Ongoing in vitro and rodent studies are examining IGF-1R signalling in Alzheimer's and Parkinson's disease models, and findings remain preliminary.
- Model organism genetics: The insulin/IGF-1 receptor pathway continues to be studied genetically in model organisms, with some groups exploring IGF-1 receptor antagonists.
- Cancer biology: IGF-1R signalling continues to be studied in specific cancer types.
For researchers interested in the broader context of peptide research, the Peptide Glossary provides definitions of related terms, and the Research Hub offers additional resources on peptide-based investigations.
Frequently Asked Questions
What is the difference between IGF-1 and IGF-1 LR3?
IGF-1 LR3 (Long R3) is a synthetic analog of IGF-1 carrying two changes, and neither of them is a truncation: arginine replaces the glutamic acid at position 3, and a 13-residue extension is added to the N-terminus. The name records both, "R3" for the arginine substitution and "Long" for the extension. This modification has been reported to reduce binding to IGFBPs, which increases the free fraction available to the receptor in vitro. However, IGF-1 LR3 is a distinct compound and should not be considered interchangeable with native IGF-1 in research contexts.
Can IGF-1 be used in cell culture experiments?
Yes, recombinant human IGF-1 is commonly used in cell culture to study proliferation, differentiation, and survival pathways. Typical media concentrations range from 10 to 100 ng/mL, though optimal concentrations should be determined empirically for each cell type. Researchers should consult their institutional biosafety guidelines before use.
Is IGF-1 the same as growth hormone (GH)?
No. Growth hormone (GH) is a 191-amino-acid peptide secreted by the pituitary gland that stimulates the liver to produce IGF-1. IGF-1 mediates much of GH receptor signalling downstream, but the two molecules have distinct structures, receptors, and signaling pathways.
IGF-2, and How the Two Differ
This page is about IGF-1. IGF-2 is the other insulin-like growth factor and is frequently confused with it, so the distinction is worth stating.
IGF-1 is a single-chain peptide of 70 amino acids across four domains (B, C, A and D), whose A and B domains share roughly 50% sequence similarity with the insulin A and B chains. IGF-2 is a 67-amino-acid single-chain polypeptide, produced mainly in the liver, and its B and A domains share a comparable similarity with insulin.
The receptor preferences differ, which is why findings about one do not transfer to the other:
| Principal receptors | Note | |
|---|---|---|
| IGF-1 | IGF-1R, with lower affinity for IGF-2R and the insulin receptor | The IGF-1R route is the one most mechanistic work describes |
| IGF-2 | High affinity for IGF-2R and IR-A; moderate for IR-B; low for IGF-1R | Also binds IR-A/IGF-1R heterodimers |
IGF-2R is the cation-independent mannose-6-phosphate receptor and is structurally unrelated to IGF-1R, despite the name.
IGF-2 is paternally expressed in the fetus and placenta, which is the main reason its developmental biology is studied separately from IGF-1's.
Circulating free IGF-1 is governed by six high-affinity binding proteins (IGFBP-1 to IGFBP-6), each around 30 kDa, so a total-IGF-1 measurement and a free-IGF-1 measurement are not the same number.
References
- Rinderknecht, E., & Humbel, R. E. (1978). "The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin." Journal of Biological Chemistry, 253, 2769–2776.
- LeRoith, D., & Yakar, S. (2007). "Mechanisms of disease: metabolic effects of growth hormone and insulin-like growth factor 1." Nature Clinical Practice Endocrinology & Metabolism, 3, 302–310.
- Adams, G. R. (2002). "Invited review: autocrine/paracrine IGF-I and skeletal muscle adaptation." Journal of Applied Physiology, 93, 1159–1167.
- Carro, E., Trejo, J. L., Busiguina, S., & Torres-Aleman, I. (2001). "Circulating insulin-like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy." Journal of Neuroscience, 21, 5678–5684.
- Kenyon, C. (2010). "The genetics of ageing." Nature, 464, 504–512.
- Clemmons, D. R. (2012). "Metabolic actions of insulin-like growth factor-I in normal physiology and diabetes." Endocrinology and Metabolism Clinics of North America, 41, 425–443.
Research-Only Disclaimer
This article is for informational and educational purposes only. IGF-1 is sold as a research compound for laboratory use only and is not approved for human consumption, veterinary use, or any therapeutic application. Volta Peptides does not supply any research peptide for administration to people or animals. All products are intended for use by qualified researchers in compliance with applicable laws and institutional guidelines. For more information, please refer to our Research Disclaimer and Quality & Testing pages.
Reviewed by the Volta Peptides Research Team
Consolidated 18 October 2026: merged from a separate IGF-1/IGF-2 introduction article.
