What Is Insulin-Like Growth Factor 2? Definition and What Research Reports

Definition

Insulin-like growth factor 2 (IGF-2) is a small, naturally occurring single-chain polypeptide hormone of roughly 67 amino acids that belongs to the insulin superfamily, alongside insulin itself and insulin-like growth factor 1 (IGF-1). It is produced endogenously in humans and other vertebrates — most abundantly by the liver, but also by placenta, muscle, bone, brain and many other tissues — and circulates bound to insulin-like growth factor binding proteins rather than freely. IGF-2 is encoded by a genomically imprinted gene, meaning expression is typically restricted to the paternally inherited allele in most tissues, and it acts through the type 1 IGF receptor, the type 2 IGF (cation-independent mannose-6-phosphate) receptor, and isoforms of the insulin receptor. In the research literature the term "IGF-2" usually refers to the native peptide hormone itself, though it also appears as part of the names of unrelated RNA-binding proteins (the IGF2BP family) that regulate IGF-2 messenger RNA.

What Class of Molecule It Is

IGF-2 is a peptide hormone, not a synthetic research peptide analogue. It is a genuine endogenous signalling molecule with a defined gene, an imprinted regulatory locus, receptor partners and circulating binding proteins. That places it in a different category from the many short synthetic sequences discussed elsewhere in peptide literature: IGF-2 is a subject of physiology and disease research rather than a designed compound.

• Type: single-chain polypeptide growth factor, insulin superfamily
• Origin: endogenous; expressed from an imprinted gene locus in numerous tissues
• Receptors studied: IGF-1 receptor, IGF-2/mannose-6-phosphate receptor, insulin receptor isoforms
• Transport: circulates complexed with IGF binding proteins
• Common research contexts: fetal and embryonic growth, neurobiology, bone remodelling, ocular tissue, tumour microenvironment

How the Term Is Used in Peptide and Biomedical Research

Across the published literature, "insulin-like growth factor 2" appears in three broad ways. First, as an endogenous ligand whose tissue concentrations are measured and correlated with an outcome. Second, as an exogenously administered protein in animal or cell-culture models, where investigators applied recombinant IGF-2 to a system and observed what changed. Third, as part of the names of the IGF2 mRNA-binding proteins (IGF2BP1–3), which are distinct molecules that bind IGF-2 transcripts and are frequently studied as candidate biomarkers; readers scanning titles should note that a paper about "IGF2BP3" is not a paper about the IGF-2 hormone.

This page is for educational purposes only and is not medical advice; consult a licensed physician about any medical question. IGF-2 is not described here as a product, and nothing below describes a protocol for use in people.

What the Published Literature Reports

Neuroscience and behaviour

Researchers examining hippocampal intracerebral hemorrhage in an animal model reported that IGF-2 regulated neuronal density and that the distribution of IGF-2 itself shifted following the hemorrhagic injury, linking the growth factor to tissue response after bleeding in the hippocampus (PMID 32912509). In a different neurological setting, a study that tested IGF-2 in both mouse and rat models of Angelman Syndrome reported that IGF-2 did not improve the behavioural deficits measured in those models, a negative result the authors framed as a caution against generalising earlier positive neurodevelopmental findings (PMID 34526125).

Appetite and central administration

An avian study reported that central administration of insulin-like growth factor-2 suppressed food intake in chicks, positioning IGF-2 among the centrally acting peptides investigated for effects on feeding behaviour (PMID 33727127). The study was conducted in chicks and its findings were not extended to humans by the authors.

Retina and insulin receptor signalling

A biochemistry study reported that IGF-2 regulated basal insulin receptor activity in the retina, describing the growth factor as a contributor to the constitutive receptor tone observed in retinal tissue rather than as a purely developmental signal (PMID 33915127). Separately, work on pterygium — a growth of conjunctival tissue over the cornea — reported a synergic action between IGF-2 and miRNA-483 in the pathogenesis of that lesion (PMID 36901760).

Bone, fat and stem-cell biology

A pharmacological sciences study reported that IGF-2 promoted osteoclastogenesis and increased inflammatory cytokine levels under hypoxic conditions, connecting the growth factor to bone-resorbing cell formation in a low-oxygen environment (PMID 35641033). In adipose-lineage work, researchers reported that IGF-2 promoted the adipogenesis of hemangioma-derived stem cells, meaning it pushed those cells toward fat-cell differentiation in culture (PMID 30867686).

Reproduction and early development

Because IGF-2 is a classical fetal growth factor, reproductive studies have measured it directly in gametes. One study examined sperm insulin-like growth factor 2 protein levels and discussed their implications for early embryo development, treating IGF-2 abundance as a candidate marker rather than an intervention (PMID 41534163).

Tumour biology and the IGF2BP proteins

In oncology, a 2024 study reported that IGF-2 drove fibroblast-mediated tumour immunoevasion and conferred resistance to immunotherapy, implicating the growth factor in how tumour-associated fibroblasts blunt immune attack (PMID 39545420). The related but distinct RNA-binding protein IGF2BP3 has been evaluated as a potential biomarker in small-cell lung cancer alongside related molecules (PMID 35845940), and another study reported that IGF2BP3 promoted kidney injury by regulating β-catenin signalling (PMID 36520532).

Where IGF-2 was reported to be dispensable

Not every model showed a requirement for IGF-2. A pediatric surgery study reported that IGF-2 and its enterocyte receptor were not required for intestinal adaptation in response to massive small bowel resection, indicating that compensatory gut remodelling proceeded without them in that model (PMID 24888844).

Summary Table of Reported Findings

Reported Effects and Safety Signals: What Studies Report

The verified literature summarised here consists of mechanistic, animal and cell-culture work rather than human safety trials, so no adverse-event profile for administered IGF-2 in people is described in these papers. Several reported biological effects are context-dependent and not uniformly favourable: researchers reported that IGF-2 increased inflammatory cytokine levels and osteoclast formation under hypoxia (PMID 35641033), and that it contributed to tumour immunoevasion and immunotherapy resistance (PMID 39545420). A separate study reported that IGF-2 failed to correct behavioural deficits in two rodent models (PMID 34526125). Taken together, the studies describe a growth factor whose reported effects varied by tissue and condition.

References

• Insulin-like growth factor 2 drives fibroblast-mediated tumor immunoevasion and confers resistance to immunotherapy (The Journal of Clinical Investigation, 2024)
• Synergic Action of Insulin-like Growth Factor-2 and miRNA-483 in Pterygium Pathogenesis (International Journal of Molecular Sciences, 2023)
• Insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of Angelman Syndrome (Molecular Autism, 2021)
• Sperm insulin-like growth factor 2 protein levels: implications for early embryo development (Reproductive BioMedicine Online, 2026)
• Insulin-like growth factor 2 promotes osteoclastogenesis increasing inflammatory cytokine levels under hypoxia (Journal of Pharmacological Sciences, 2022)
• Insulin-like growth factor 2 promotes the adipogenesis of hemangioma-derived stem cells (Experimental and Therapeutic Medicine, 2019)
• Insulin-like growth factor-2 regulates basal retinal insulin receptor activity (The Journal of Biological Chemistry, 2021)
• Central administration of insulin-like growth factor-2 suppresses food intake in chicks (Neuroscience Letters, 2021)
• Insulin-Like Growth Factor 2 mRNA-Binding Protein 3 and Its Related Molecules as Potential Biomarkers in Small-Cell Lung Cancer (BioMed Research International, 2022)
• Insulin-like growth factor 2 mRNA-binding protein 3 promotes kidney injury by regulating β-catenin signaling (JCI Insight, 2023)
• Insulin-like growth factor 2 and its enterocyte receptor are not required for adaptation in response to massive small bowel resection (Journal of Pediatric Surgery, 2014)
• Insulin-Like Growth Factor 2 (IGF-2) Regulates Neuronal Density and IGF-2 Distribution Following Hippocampal Intracerebral Hemorrhage (Journal of Stroke and Cerebrovascular Diseases, 2020)