IGF-2
Insulin-like growth factor 2, IGF-II, somatomedin A (historical)
1What it is
IGF-2 is the lesser-known sibling of IGF-1. Both are small proteins structurally related to insulin, and both circulate bound to IGF-binding proteins. In humans IGF-2 is actually the more abundant of the two in adult blood, at roughly three times the concentration of IGF-1, but unlike IGF-1 it is only weakly controlled by growth hormone. Its best-understood role is in fetal growth: the IGF2 gene is "imprinted", expressed only from the paternal copy, and disturbances in that region of chromosome 11 cause either growth restriction (Silver-Russell syndrome) or overgrowth with tumour predisposition (Beckwith-Wiedemann syndrome). Mice lacking the gene are born at 60% of normal size (DeChiara 1990, Nature).
In adults IGF-2 is produced by the liver and many tissues, acts locally in muscle, bone and brain, and is overproduced by some tumours — the cause of a well-recognised but rare syndrome of severe hypoglycaemia from "big IGF-2" secreted by large sarcomas and other tumours (Daughaday 1988, NEJM).
IGF-2 has never been developed as a medicine. Interest as a research compound comes mainly from a decade of rodent work on memory, and from muscle-regeneration biology. Human data on administering it do not exist, and this profile is short for that reason.
2How it's thought to work
3What the research shows
Memory enhancement in rodents
Muscle regeneration
Cancer biology
Body composition, longevity, recovery in humans
4Reported side effects and interactions
Literature-reported
no human administration data. The human syndromes of IGF-2 excess (tumour-associated) feature profound hypoglycaemia, suppressed GH and insulin, and growth of soft tissue. Rodent studies at memory-enhancing doses report no gross toxicity over short courses.Community-reported
scarcely any; the compound is rarely used and reports are unreliable. Hypoglycaemia symptoms would be expected.Theoretical. the strongest theoretical concern on this site for a growth factor — IGF-2 signalling through IGF-1R and IR-A is a recognised driver of tumour growth, and loss of IGF2 imprinting is an early event in several cancers. Hypoglycaemia via IR-A. Possible suppression of endogenous GH/IGF-1.
Interactions. additive hypoglycaemia with insulin, sulfonylureas, IGF-1 variants and GLP-1 .
Markers researchers commonly monitor
No compound-specific monitoring exists; the following derive from IGF physiology:
| Marker | Why it's watched |
|---|---|
| Fingerstick glucose around dosing and fasting glucose | hypoglycaemia is the acute, predictable risk. |
| IGF-1, IGF-2 and IGFBP-3 | serum IGF-2 can be measured by specialist labs; a baseline is informative because endogenous levels are high and variable. |
| HbA1c and fasting insulin | longer-term glucose handling. |
| CBC and CMP | general baseline for an injected growth factor with no human safety data. |
| Age-appropriate cancer screening | the mechanism warrants it; this is a clinician conversation. |
Free for everyone. Safety information is never behind a paywall.
5Reconstitution and handling
Supplied, where it is at all, as small (often 100 µg–1 mg) vials intended for laboratory use, frequently with a recommended such as dilute acetic acid or a buffer rather than . gently against the vial wall and keep cold. Laboratory-grade growth factors are not manufactured to injectable standards.
Open in calculator, pre-loaded →6Commonly studied alongside
IGF-1 and IGF-1 LR3 (as comparators in binding and potency work), mecasermin (approved IGF-1), insulin (receptor pharmacology). In the memory literature, compared with other consolidation enhancers in rodents; no human combinations.
Informational cross-links. Not stack recommendations.
7Regulatory status by region
| Region | Status (checked —) |
|---|---|
| United States | Not FDA-approved; not a compounding-list substance; sold only as a laboratory reagent |
| European Union | Not authorised |
| United Kingdom | Not licensed |
| Australia | Not approved; growth factors of this class are prescription-only † |
| South Africa | Not registered |
| Sport | Prohibited by WADA (S2 — "insulin-like growth factor-1 (IGF-1) and its analogues" and growth factors affecting muscle, tendon or ligament are listed; IGF-2 falls under the growth-factor wording) † |
8Open questions
- Whether the rodent memory effect has any human counterpart; no trial has been attempted and the safety case for one is difficult.
- The real-world composition and purity of IGF-2 sold outside laboratory supply chains.
- Everything about human pharmacokinetics and safety.
9References
- 1DeChiara TM, Efstratiadis A, Robertson EJ (1990). A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting. Nature. PubMed · DOI
- 2Daughaday WH et al. (1988). Synthesis and secretion of insulin-like growth factor II by a leiomyosarcoma with associated hypoglycemia. N Engl J Med. PubMed · DOI
- 3Chen DY et al. (2011). A critical role for IGF-II in memory consolidation and enhancement. Nature. PubMed · DOI
- 4Stern SA, Kohtz AS, Pollonini G, Alberini CM (2014). Enhancement of memories by systemic administration of insulin-like growth factor II. Neuropsychopharmacology. PubMed · DOI
- 5Steinmetz AB et al. (2018). Insulin-like growth factor II targets the mTOR pathway to reverse autism-like phenotypes in mice. J Neurosci. PubMed · DOI
- 6Florini JR et al. (1991). "Spontaneous" differentiation of skeletal myoblasts is dependent upon autocrine secretion of insulin-like growth factor-II. J Biol Chem. PubMed
- 7Constância M et al. (2002). Placental-specific IGF-II is a major modulator of placental and fetal growth. Nature. PubMed · DOI
- 8Livingstone C (2013). IGF2 and cancer. Endocr Relat Cancer. PubMed · DOI
† Being confirmed by our reviewers against current sources.
10Community
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Self-reported side effects Phase 2
11Page history
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