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IGF-1 Research: The Binding Proteins Decide
Almost none of it circulates free. What reaches a receptor depends less on how much is present than on what is holding it.
In short
Most IGF-1 research is really research into the binding proteins. Almost none of the circulating pool is free, so what reaches a receptor is governed less by how much is present than by what is holding onto it. Treating IGF-1 as a simple ligand is the commonest way to misread the system.
What IGF-1 research is actually measuring
Insulin-like growth factor 1 is a single-chain polypeptide of 70 amino acids with a molecular weight near 7,650 daltons. Structurally it resembles proinsulin, which is where the name comes from.
In circulation, however, it does not travel alone. The overwhelming majority is captured by a family of binding proteins, and that changes the question a study is really asking.
A protein, not a peptide
At roughly 7.6 kilodaltons, IGF-1 is an order of magnitude larger than the short peptides sold alongside it. BPC-157 is fifteen residues; GHK-Cu is three.
That size difference has a practical consequence. A 1mg vial of IGF-1 contains far fewer molecules than a 1mg vial of a small peptide, so equal-mass comparisons between them are meaningless. Our guide to molecular weight and moles covers why.
Size also changes how it behaves physically. Larger proteins adsorb to surfaces more readily and aggregate more easily, which matters at the dilutions typical of cell work.
The binding proteins are the system
Six insulin-like growth factor binding proteins exist, and IGFBP-3 carries most of the circulating load. It does so as part of a ternary complex with an acid-labile subunit, producing an assembly of roughly 150 kilodaltons.
Something in the region of 98 per cent of circulating IGF-1 sits in that bound state at any moment. The complex extends its half-life dramatically and, at the same time, keeps it away from receptors until released.
Therefore binding-protein availability, not total concentration, is frequently the variable that actually moves an outcome. A change in IGFBP-3 can alter free ligand without any change in total IGF-1 at all.
Receptors, and the one next door
The primary target is IGF-1R, a receptor tyrosine kinase assembled as an alpha-two beta-two heterotetramer. Binding triggers autophosphorylation and recruits the usual downstream cascades.
IGF-1R is closely related to the insulin receptor, and the two can form hybrid receptors in tissues expressing both. IGF-1 also binds the insulin receptor itself, though with far lower affinity.
As a result, interpreting a signal as purely IGF-1R mediated requires care. The receptors overlap, and so do their outputs.
Why IGF-1 research often uses modified analogues
Because the binding proteins dominate, several analogues exist specifically to escape them. The best known carries an amino-acid substitution near the N-terminus plus a short N-terminal extension, which together sharply reduce binding-protein affinity.
Consequently an analogue and the native protein are not interchangeable in a protocol, even at matched mass. They differ in the one property the system is built around.
Which form a given vial contains is a question for the product page and the certificate of analysis rather than an assumption.
Handling a 7.6 kDa protein
Reconstitute gently, down the vial wall, without shaking. Proteins of this size foam and aggregate more readily than short peptides, and foaming is difficult to reverse.
Keep stocks cold, aliquot rather than repeatedly freeze-thawing, and expect adsorption losses in dilute solution. Our solubility guide covers the aggregation side in more detail.
IGF-1 research: frequently asked questions
Is IGF-1 a peptide or a protein?
It sits at the boundary and is usually described as a polypeptide or small protein. At 70 residues and about 7,650 daltons it is far larger than the short synthetic peptides it is sold alongside, and it behaves more like a protein when handled.
Why does so little of it circulate free?
Because the binding proteins are abundant and bind tightly. Roughly 98 per cent is complexed, mostly with IGFBP-3 together with an acid-labile subunit. The complex greatly extends half-life while keeping the ligand away from receptors until it is released.
What is the difference between native IGF-1 and an analogue like LR3?
The analogues are modified specifically to reduce binding-protein affinity, using an amino-acid substitution near the N-terminus plus a short extension. That single change alters the property the whole system turns on, so the two are not interchangeable at matched mass.
Does IGF-1 act on the insulin receptor?
It can, at much lower affinity than at IGF-1R. Hybrid receptors combining subunits of both also occur in tissues expressing the two. This overlap is why attributing an observed effect cleanly to one receptor takes deliberate controls.
Why is it supplied in 1mg vials when peptides come as 10mg?
Because of molecular weight. One milligram of a 7,650 dalton protein contains roughly a tenth the number of molecules as one milligram of a 765 dalton peptide, so the vial sizes reflect molar quantity rather than a difference in value.
Related products
IGF-1 1mg. Reconstitute with Hospira Bacteriostatic Water 30ml. Certificates of analysis are published on the COA page.
References
The sources below are indexed on PubMed, and compound records are held at PubChem.
- Rinderknecht E, Humbel RE. The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. Journal of Biological Chemistry — the original sequence determination.
- Firth SM, Baxter RC. Cellular actions of the insulin-like growth factor binding proteins. Endocrine Reviews — on the IGFBP family and the ternary complex.
- LeRoith D, Roberts CT. The insulin-like growth factor system and cancer. Cancer Letters — on IGF-1R signalling and receptor overlap with the insulin receptor.
Research use only. Every product referenced here is sold strictly for in-vitro laboratory research. Nothing on this page is medical advice, and none of these compounds are approved for human or veterinary use, diagnosis or treatment.
[…] Growth hormone does much of its work indirectly, through insulin-like growth factor 1. For what happens downstream of this axis, see our guide to IGF-1 and its binding proteins. […]