Insulin-like Growth Factor 1 (IGF1 Human) is a 70-amino-acid polypeptide hormone with structural similarity to insulin. It plays a critical role in growth regulation, metabolic function, and cellular repair. Produced primarily by the liver under stimulation by growth hormone (GH), IGF1 circulates bound to insulin-like growth factor-binding proteins (IGFBPs), which modulate its bioavailability . IGF1 is essential for postnatal development, skeletal muscle hypertrophy, and tissue regeneration, while dysregulation is linked to cancer, neurodegenerative diseases, and metabolic disorders .
Mechanism: IGF1 binding induces autophosphorylation of tyrosine residues on IGF1R, triggering downstream signaling cascades (e.g., PI3K/Akt and MAPK pathways) .
Dimerization: Cryo-EM studies reveal an asymmetric Γ-shaped IGF1R dimer bound to a single IGF1 molecule, hindering cooperative binding of a second ligand .
Feature | IGF1 Receptor (IGF1R) | Insulin Receptor |
---|---|---|
Homology | 60% with insulin receptor | - |
Ligand Affinity | Binds IGF1, IGF2, insulin | Primarily binds insulin |
Signaling Pathways | PI3K/Akt, MAPK | PI3K/Akt, MAPK |
Functional Role | Growth, survival | Glucose homeostasis |
Growth and Development: Mediates GH-dependent postnatal growth; knockout mice exhibit severe growth retardation .
Muscle Maintenance: Promotes skeletal muscle satellite cell proliferation and differentiation, preventing atrophy .
Metabolic Regulation: Enhances GLUT4 expression and insulin-stimulated glucose uptake in human myotubes .
Cancer: Elevated IGF1 levels correlate with increased risk of prostate, breast, and colorectal cancers .
Neurodegeneration: Dual role in Alzheimer’s and Parkinson’s diseases:
Cardiovascular Disease: Low IGF1 levels linked to atherosclerosis and heart failure .
Therapeutic Use: Mecasermin (synthetic IGF1) treats growth failure in children with severe IGF1 deficiency .
Clinical Trials:
Condition | Study Outcome | Reference |
---|---|---|
ALS | No significant survival benefit | |
Preterm Brain Injury | Reduced neurodevelopmental deficits | |
Muscle Atrophy | Enhanced myotube differentiation |
Protein Intake: Dairy protein (milk, yogurt) increases circulating IGF1 levels, while cheese shows no effect .
Fiber and Wholegrains: Positive correlation with IGF1, potentially via gut microbiome-derived short-chain fatty acids .
In Vitro Myotube Models: IGF1 supplementation enhances human myotube contractility, oxidative metabolism, and insulin sensitivity .
Animal Studies: IGF1R inhibition in mice mimics preterm brain injury, highlighting IGF1’s role in neurodevelopment .
The somatomedins, also known as insulin-like growth factors (IGFs), are a family of peptides that play a crucial role in the growth and development of mammals. IGF1 is a key mediator of growth hormone's (GH) growth-promoting effects. Initial research revealed that GH did not directly stimulate sulfate incorporation into cartilage. Instead, it acted through a serum factor initially called 'sulfation factor' and later renamed 'somatomedin.' Three primary somatomedins have been identified: somatomedin C (IGF1), somatomedin A (IGF2), and somatomedin B.
Recombinant Human IGF1 produced in E. coli is a single, non-glycosylated polypeptide chain consisting of 70 amino acids. It has a molecular weight of 7.6 kDa. The purification of IGF-1 is achieved using proprietary chromatographic methods.
The protein was freeze-dried from a concentrated solution in phosphate-buffered saline (PBS) at a pH of 7.0.
Lyophilized IGF1 remains stable at room temperature for up to 3 weeks. However, for long-term storage, it is recommended to store it in a desiccated state at a temperature below -18°C. After reconstitution, IGF1 should be stored at 4°C for 2 to 7 days. For extended storage, it is advisable to add a carrier protein such as HSA or BSA at a concentration of 0.1%. Avoid repeated freeze-thaw cycles.
The purity of IGF-1 is greater than 97.0%, as determined by the following methods:
(a) Reverse-phase high-performance liquid chromatography (RP-HPLC) analysis.
(b) Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis.
The biological activity, assessed using a cell proliferation assay with serum-free human MCF-7 cells, is less than 2 ng/ml. This corresponds to a specific activity greater than 5.0 x 105 IU/mg.
Somatomedin C, IGF-I, IGFI, IGF1, IGF-IA MGF.
IGF-1 is a single-chain polypeptide consisting of 70 amino acids with a molecular weight of approximately 7.6 kDa . It shares a high degree of homology with proinsulin, which is reflected in its ability to bind to insulin receptors, albeit with lower affinity . The primary function of IGF-1 is to mediate the effects of growth hormone, promoting growth and development in tissues such as muscle, bone, and cartilage .
Recombinant human IGF-1 is produced using recombinant DNA technology, typically in Escherichia coli (E. coli) expression systems . This method involves inserting the human IGF-1 gene into the bacterial DNA, allowing the bacteria to produce the protein. The recombinant protein is then purified and used for various research and therapeutic applications.
Recombinant human IGF-1 is typically lyophilized and stored at -20°C to -80°C to maintain its stability . It is essential to avoid repeated freeze-thaw cycles to prevent degradation of the protein. Once reconstituted, the protein should be stored under sterile conditions at 2°C to 8°C for short-term use or at -20°C to -80°C for long-term storage .