IGF-1 stands for insulin-like growth factor 1, which is often sold under the name somatomedin C. This is a protein that is encoded by the IGF1 gene in humans, though it is seen in other forms in a variety of types of animals. This peptide is commonly referred to as the sulfation factor which creates non-suppresible insulin-like activity.
IGF-1 has taken on this name because it is has a molecular structure that is very similar to insulin and acts in a very similar way to this chemical. Natural versions of IGF-1 contain 70 amino acids that are aligned in a single chain.
IGF-1 is largely produced in the liver with endocrine hormones and can target tissues using autocrine and paracrine mechanisms. This is stimulated by growth hormone, though can be limited by a lack of growth hormone receptors, under nutrition or failure of the signaling pathways downstream of the signaling pathway. IGF-1 is almost always bound with the binding proteins of IGFBP-3 which is one of the most abundant proteins in this synthesis.
In rats IGF-1 was found to be associated with dietary casein and having a negative association of protein-free diets. Plants have been found to contain biologically active recombinant IGF-1, which was noted in transgenic rice grains.
Role in Muscle Repair
New studies have indicated that IGF-1 is vital to repairing and regenerating muscle tissue in animals.
- Skeletal muscle is a highly dynamic tissue that is designed to respond to external and endogenous stimuli which includes mechanical loading, growth factors and alterations. Soleus muscle in particular is found to express muscular atrophy then the muscles are not used or extensively damaged.
- IGF-1 has been implicated as a regulator in muscle modulation and repair, including controlling muscle size in animals. This was examined for a viral mediated overexpression of this peptide on soleus muscle following the immobilization of the hind limb upon reloading in mice.
- During this process recombinant cDNA viruses containing IGF-1 were injected into the posterior hind limbs of the test subjects and the contralateral limb was simultaneously provided with an application of saline.
- At 20 weeks the hind limbs of the mice were immobilized for two weeks as a means of inducing atrophy in the ankle plantar flexor and soleus muscles. The mice were then allowed to reambulate and the recovery of these tissues was monitored for up to 21 days.
- Initial findings revealed that overexpression of IGF-1 were attenuated with the reloading induced damage of the soleus muscles. This was used by the mouse’s body to accelerate regeneration to force recovery of the muscles. MRI scans of the nice also showed that markers of muscle damage were lower in those that were injected with IGF-1 in the soleus muscles at the 2-5 day market after reambulation.
The reduction of the prevalence of damage to the muscles after an application of IGF-1 was confirmed via histology. This showed a lower fraction of abnormal muscle tissue in the areas that were exposed to IGF-1 2 days after reambulation occurred.
The evidence that IGF-1 assists with muscle regeneration showed timely increases in the central nuclei including a paired box transcription factor, elevated MyoD mRNA and embryonic myosin. This helps to demonstrate that IGF-1 may have potential in protecting skeletal muscle from damage by increasing regeneration and repair of the tissues.
Mechanism of Action
The actions of IGF-1 are primarily mediated by the receptors it binds to, allowing it to interact with a wide variety of tissues and cell types in animal bodies.
- Binding to different activators of AKT signaling pathways can stimulate cell proliferation or growth. It is also found to be a mediator of growth hormone effects from the anterior pituitary gland, which in turn moves from the bloodstream to the liver to trigger the production of IGF-1. It has also been seen to inhibit programmed cell death.
- Animal tissues throughout the body in a variety of different species have been found to interact with IGF-1 including cartilage, skeletal muscle, kidneys, liver, skin, nerves, lungs, hematopoietic cells and others. This peptide can be used to create effects similar to insulin, control the development and growth of cells and synthesize DNA. This is particularly seen in nerve cells.
- Deficiencies of IGF-1 or the presence of growth hormone have been shown to cause animals to display a diminished stature, though supplying animals with recombinant growth hormone or IGF-1 in clinical trials has been found to help increase their size. Researchers hope to continue to research this potential to develop a treatment for plan for conditions such as Laron syndrome. Research has also been found to improve these conditions in cattle and IGF-1 has been found to help improve reproduction in these animals.
IGF-1R and growth factor receptors can be triggered using multiple pathways. PI3K has been found to be an influential downstream partner in mammals, acting as a target for rapamycin. The full interaction of these receptors is still being investigated.
Receptors and Binding
IGF-1 has been found to bind with two surface receptors, though research is still ongoing to determine other connective points.
- IGF-1 may bind to insulin receptors as well as IGF1R. The latter appears to have physiologic effects that have an increased affinity for IGF-1 rather than those that are bound to the insulin receptors.
- Both of these receptors are a tyrosine kinase that causes phosphate molecules to be added to certain tyrosines. IGF-1 will also activate insulin receptors at around .1 times the potency of insulin. Part of this signaling response may be caused by IGF1R insulin receptor heterodimers that bind with insulin 100 fold less effectively. This has not been shown to correlate with the true potency of IGF-1 in vivo. This is also not effective in inducing phosphorylation of insulin receptors.
- IGF-1 production is seen throughout an animal’s life but production is highest during an animal’s pubertal growth spurt with levels gradually reducing as the animal reaches old age.
- Other IGFBP molecules take on an inhibitory role when interacting with these peptides. IGFBP-2 and 5 can bind with IGF-1 with a higher affinity than the bindings at the receptors. This is used by an animal’s body to increase serum levels of these chemicals to decrease the activity of IGF-1 when there is no longer a need for this peptide.
IGF-1 has been found to be closely related to IGF-2 which can bind with the same receptors, though IGF-2 can also bind with IGF-2 receptors. IGF2R receptors do not have the signal transduction capacities that allow it to sync with IGF-1 to make this protein more available, so it will often bind with IGF-1R.
Like the name implies, IGF-1 is related to insulin due to its structural properties. It is capable of acting with insulin receptors though it is not nearly as effective in this capacity as traditional insulin. Splice variants of IGF-1 are identical at the mature region but have different E domains as MGF.
IGF-1 is found to be naturally prevalent as animals are developing the proper tissues and structure the animal’s unique physiology requires. This peptide is also found to be used by adult animals for anabolic mechanisms. Synthetic versions of IGF-1 have been found to have a mecasermin that has potential in managing growth failure, though research is still ongoing to determine the best ways of utilizing this property.