IGF-1

IGF-1 (Insulin-like Growth Factor 1, formerly somatomedin C) is a 70-amino-acid polypeptide (7.65 kDa) structurally homologous to insulin (~50% sequence identity on A and B chains), synthesised primarily by the liver under growth hormone (GH) stimulation via the hypothalamic-pituitary-hepatic axis. It is the major endocrine mediator of GH anabolic effects on tissue growth, cell proliferation and metabolic homeostasis.

Structure and transport. IGF-1 circulates mainly bound (>99%) to a family of six binding proteins (IGFBP-1 to IGFBP-6, IGFBP-3 being dominant 75% of pool), themselves associated with an acid-labile subunit (ALS) forming a 150 kDa ternary complex. This complex regulates bioavailability, extends plasma half-life (15 h vs ~10 min for free IGF-1) and modulates activity on target tissues.

Mechanism of action. IGF-1 activates the IGF-1R tyrosine kinase receptor (ubiquitously expressed) via dimerisation, autophosphorylation and recruitment of IRS-1/2 substrates → PI3K/AKT/mTOR (survival, protein synthesis, hypertrophy) and RAS/RAF/MEK/ERK-MAPK (proliferation, differentiation). At high concentration it can activate the insulin receptor (IR) and IR/IGF-1R hybrid receptors. IGF-1R is also implicated in several cancers (prostate, breast, colon), motivating development of anti-IGF-1R inhibitors.

IGF-1 in clinic and research. Serum IGF-1 assay is the standard biomarker to evaluate response to GH stimulation (GHRH, GHRP, CJC-1295, ipamorelin, MK-677, sermorelin, tesamorelin) in preclinical and clinical studies on the somatotropic axis. Mecasermin (recombinant IGF-1, Increlex®) is FDA/EMA approved for severe primary IGF-1 deficiency. At lab-peptides-france.com, IGF-1 in IGF-1 LR3 form (Long-R3, extended half-life analogue) is marketed for preclinical research on muscle hypertrophy and healing.