IGF-1

Insulin-like growth factor 1 (IGF-1) is a peptide hormone primarily produced by the liver in response to growth hormone (GH) that mediates growth, cellular proliferation, differentiation, and survival throughout the body. PMID 33557137PMID 33962049 It also functions in an autocrine and paracrine manner when produced locally in various tissues. PMID 40442384PMID 23148873

IGF-1 exerts its biological effects by binding to the type 1 IGF-1 receptor (IGF1R), a receptor tyrosine kinase that activates downstream signaling pathways, predominantly the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways. PMID 40442384 These pathways regulate cellular anabolism, protein synthesis, and cell survival. PMID 8874492 In circulation, approximately 98% of IGF-1 is bound to IGF binding proteins (IGFBPs), which modulate its bioavailability and tissue access. PMID 33557137PMID 33962049 Beyond its well-established role in promoting postnatal growth—contributing to approximately 83% of postnatal growth when combined with GH's direct effects—IGF-1 influences glucose metabolism, has neuroprotective and cardioprotective properties, and plays roles in neurogenesis and synaptic plasticity. PMID 36848915PMID 40442384PMID 21042815

IGF-1 is considered an exerkine, a molecule released in response to exercise that mediates beneficial adaptations to physical activity. PMID 20010132PMID 20010131 The evidence supporting this classification includes that local IGF-1 production is consistently upregulated with both acute and chronic exercise. PMID 20010131 IGF-1 appears to play a central role in exercise-induced cellular anabolism, muscle and bone remodeling, and body composition changes. PMID 20010132PMID 20010131 While circulating IGF-1 levels may decrease or remain unchanged with certain training regimens, local tissue production increases, suggesting that locally produced IGF-1 is particularly important for mediating exercise adaptations. PMID 20010131 The IGF-1 system has been described as "an important and central hormonal axis that plays a significant role concerning cellular anabolism" in the context of physical activity. PMID 20010132

Growth disorders represent the most established therapeutic application. IGF-1 (mecasermin) is FDA-approved for treating growth failure in pediatric patients with severe primary IGF-1 deficiency or growth hormone gene deletion who have developed neutralizing antibodies to growth hormone. (PMID: FDA Orange Book) Clinical studies demonstrate that recombinant human IGF-1 effectively promotes linear growth in children with growth hormone insensitivity syndrome (GHIS), including Laron syndrome, though it does not fully restore normal growth rates compared to growth hormone replacement in GH deficiency. PMID 15231299PMID 19198769PMID 36446332

Metabolic and insulin-resistant conditions show significant promise. IGF-1 improves glycemic control in both type 1 and type 2 diabetes mellitus by enhancing insulin sensitivity and reducing glucose levels. PMID 8116999PMID 15231299PMID 15860416 In patients with non-insulin-dependent diabetes, IGF-1 reduced fasting blood glucose by approximately 30% and serum insulin concentrations by more than 50%, while substantially decreasing triglyceride levels. PMID 22682639PMID 7821734 IGF-1 has also proven effective in severe insulin resistance syndromes. PMID 15231299PMID 22682639PMID 7821734

Anabolic and catabolic conditions represent another therapeutic avenue. IGF-1's protein-sparing and anabolic properties are being evaluated for osteoporosis, catabolic states (burns, post-operative recovery, AIDS muscle wasting), chronic inflammatory disorders (Crohn's disease, cystic fibrosis), and nutritional disorders. PMID 8116999PMID 19198769PMID 18031115

Central nervous system disorders are emerging targets. IGF-1 stimulates neuronal survival and myelin synthesis, with preclinical and clinical studies showing potential efficacy in autism spectrum disorder, Alzheimer's disease, amyotrophic lateral sclerosis, spinal cord injury, and other neurodevelopmental conditions. PMID 19198769PMID 26780584

Liver cirrhosis and aging-related conditions have been identified as states of IGF-1 deficiency where replacement therapy may provide clinical benefit. PMID 23148873

The most common adverse effects include hypoglycemia (controlled by administration with meals), lymphoid tissue hyperplasia, body fat accumulation, and facial coarsening. PMID 19198769 Long-term safety concerns include IGF-1's anti-apoptotic properties and potential cancer risk. PMID 19198769