Insulin-like Growth Factor 1 (IGF-1): What the Published Literature Describes

What IGF-1 Is

Insulin-like growth factor 1 (IGF-1, historically called somatomedin C) is a small peptide hormone structurally related to proinsulin. It is produced largely by the liver in response to pituitary growth hormone (GH), circulates bound to IGF-binding proteins, and also acts locally in tissues where it is made. Because it carries out much of GH's downstream signal, endocrinologists often describe the pair as the GH–IGF-1 axis, and circulating IGF-1 is used in clinical practice as an integrated marker of GH activity.

Its receptor, the IGF-1 receptor, is a tyrosine kinase closely related to the insulin receptor. Reviews of IGF-1 signalling have described activation of the PI3K/AKT and MAPK pathways and overlap with insulin signalling in glucose metabolism, including in the context of colorectal cancer biology (PMID 34208601). That structural and functional overlap with insulin is why IGF-1 appears in both growth research and metabolic research.

Key features described in the literature

• Source: mainly hepatic, GH-dependent, with local paracrine production in muscle, bone and other tissues.
• Transport: bound to IGF-binding proteins, which modulate availability.
• Signalling: IGF-1 receptor activation converging on PI3K/AKT and MAPK, with reported crosstalk into glucose metabolism (PMID 34208601).
• Clinical use of the measurement: serum IGF-1 as a screening and monitoring marker in GH excess states such as acromegaly (PMID 30855849).

IGF-1 in Growth and Early Development

Much of the interest in IGF-1 comes from developmental biology. Work in undernourished infant mice reported that microbe-mediated stimulation of intestinal NOD2 improved linear growth, linking gut microbial signals to the somatic growth axis (PMID 36821686). Researchers have used such models to ask why nutritional deficits blunt growth even when growth hormone is present.

In neonatal medicine, low circulating IGF-1 has been examined as a marker of risk. A study in preterm newborns reported an association between low IGF-1 levels and morbidity in that population (PMID 39808555). A separate review asked how IGF-1 correlates with retinopathy of prematurity, summarising evidence that IGF-1 status relates to abnormal retinal vessel development in preterm infants (PMID 35126574). These are observational and mechanistic literatures; they describe associations rather than establishing that correcting a laboratory value changes outcomes.

IGF-1 and Glucose Metabolism

Because IGF-1 and insulin share receptor family and downstream pathways, the two systems are studied together. A review of IGF-1 signalling in glucose metabolism described how the pathway intersects with cellular glucose uptake and tumour metabolism in colorectal cancer (PMID 34208601). In a clinical setting, researchers examined IGF-1 and glucose dysregulation in young adults with β-thalassemia major and discussed whether the relationship reflected causality or a potential link (PMID 36533767), a framing that captures the main difficulty in this field: IGF-1 is both an input to and an output of metabolic state.

IGF-1 also appears in reproductive endocrinology. A review of polycystic ovary syndrome and depression discussed shared biological links and potential targets across insulin resistance and related growth-factor signalling (PMID 34642910).

IGF-1 Excess and Deficiency: What Studies Report

The clearest human picture of chronic IGF-1 elevation comes from GH-secreting pituitary tumours. Clinical reviews of gigantism and acromegaly described the consequences of sustained GH and IGF-1 excess, including acral and soft-tissue overgrowth and systemic complications, and reported that IGF-1 measurement is central to diagnosis and follow-up (PMID 30855849). A review of management beyond surgery outlined medical and radiotherapy options used when surgery does not normalise hormone levels in acromegaly (PMID 23961470).

At the other end, low IGF-1 accompanies states of energy deficit. A review of anorexia nervosa and osteoporosis reported that low IGF-1 is part of the hormonal profile associated with impaired bone formation and low bone density in that illness (PMID 33666707). Low IGF-1 has likewise been reported as a marker associated with morbidity in preterm infants (PMID 39808555) and has been examined alongside glucose dysregulation in β-thalassemia major (PMID 36533767).

IGF-1 Signalling and Aging

Reduced signalling through insulin/IGF-1-like pathways has extended lifespan in several model organisms, and researchers continue to probe what that requires. A 2025 preprint reported that the longevity effects of reduced IGF-1 signalling depended on the stability of the mitochondrial genome (PMID 40501628). As a preprint, that work had not completed peer review at the time of posting, and model-organism lifespan findings do not translate directly to humans.

IGF-1-Derived and IGF-1-Adjacent Therapeutics

One approved drug traces its structure to IGF-1: trofinetide, a synthetic analogue of the IGF-1 N-terminal tripeptide glycine-proline-glutamate, received its first approval for Rett syndrome, as summarised in a drug-approval review (PMID 37191913). Separately, in the sports-supplement literature, a preliminary investigation examined multiple acute turkesterone doses against indirect measures of hypertrophy and metabolic measures (PMID 40757520); the study was described by its authors as preliminary.

How to Read This Literature

1. Association is not mechanism. Many human IGF-1 findings are cross-sectional; low or high values often reflect nutrition, illness severity or organ function.
2. Context changes interpretation. IGF-1 falls with undernutrition and rises with GH excess, so the same number means different things in different clinical settings (PMID 30855849).
3. Model organisms are not people. Lifespan and growth findings in mice and invertebrates (PMID 36821686, PMID 40501628) generate hypotheses, not human conclusions.

This page is for educational purposes only and is not medical advice; consult a licensed physician about hormone testing, symptoms or any treatment decision. Nothing here describes a protocol, and IGF-1 preparations are prescription or research-use materials depending on jurisdiction.

References

• Insulin-Like Growth Factor 1 (IGF-1) Signaling in Glucose Metabolism in Colorectal Cancer (International Journal of Molecular Sciences, 2021)
• Gigantism and Acromegaly (StatPearls)
• Acromegaly: Beyond surgery (Indian Journal of Endocrinology and Metabolism, 2013)
• Microbe-mediated intestinal NOD2 stimulation improves linear growth of undernourished infant mice (Science, 2023)
• Low levels of insulin-like growth factor 1 (IGF-1) and morbidity in preterm newborns (Andes Pediatrica, 2023)
• How is insulin-like growth factor-1 correlated with retinopathy of prematurity? (Journal of Research in Medical Sciences, 2021)
• Anorexia Nervosa and Osteoporosis (Calcified Tissue International, 2022)
• Insulin-Like Growth Factor-1 (IGF-1) and Glucose Dysregulation in Young Adult Patients with β-Thalassemia Major (Acta Biomedica, 2022)
• PCOS and Depression: Common Links and Potential Targets (Reproductive Sciences, 2022)
• Trofinetide: First Approval (Drugs, 2023)
• The longevity effects of reduced IGF-1 signaling depend on the stability of the mitochondrial genome (bioRxiv, 2025)
• The Effects of Multiple Acute Turkesterone Doses on Indirect Measures of Hypertrophy and Metabolic Measures (Muscles, 2024)