Research study from DAT's board. Info contained is his knowledge
Potency in vitro does not necessarily correlate with "effect" in vivo. An IGF-1 needs to be capable of binding to a binding protein to have a significant effect (IMO)
We'll use the following study to learn, Insulin-like growth factor (IGF)-binding proteins inhibit the biological activities of IGF-1 and IGF-2 but not des-(1-3)-IGF-1, Marina ROSS, Biochem. J. (1989) 258, 267-272
The title makes des seem very active, but,
Many cell types secrete insulin-like growth factor (IGF)-binding proteins that can be expected to sequester free IGF and modify the biological activities of the growth factors.
So what you have are cells throughout the body and they are surrounded by what is called a matrix which keeps them in place and to some extent limits access to the cell membrane (like mortar between bricks) where the IGF-1 receptor resides.
You also have IGF binding proteins of various types. Depending on the type and on the circumstance they can either increase or decrease eventual IGF-1 activity. When they bind to IGF-1 they preserve its life and render it inactive, for the most part. So bound IGF-1 is simply a complex w/ a longer life potentially and no biological activity.
Now IF this binding occurs near the site where IGF-1 needs to act, such as injured muscle we end up with a complex outside the cells waiting... like a spaceship orbiting (not really but you get the idea). If the cell bound that IGF-1 w/ a binding protein such as IGF binding protein-3 then the IGF-1 will often unbind and be pulled (attracted) to the IGF-1 receptor on the cell membrane. IGF-1 has a greater affinity (attraction) for the IGF-1 receptor then that particular binding protein.
So injured cells can secrete binding protein to trap and hold for use the free IGF-1 that travels by.
But it can also send a binding protein to keep the IGF away... like repellant. Maybe a different binding protein or other factors are involved such as the failure to breakdown the extra-cellular matrix for penetration.
A binding protein purified from bovine kidney (MDBK) cells potently inhibited the ability of IGF-2 to stimulate DNA synthesis or protein accumulation as well as to reduce rates of protein breakdown in chick embryo fibroblasts... Since the chick embryo fibroblasts contain only the type 1 IGF receptor, the MDBK-cell binding protein must have reduced the accessibility of IGF-2 and IGF- 1 to that receptor.
See it repels potentially harmful actions.
But sometimes it repels and decreases activity and other times it attracts and increases activity. See:
Inhibiting effects on both protein breakdown responsiveness to IGF and IGF binding to cell receptors were also observed with human amniotic fluid binding protein... These results contrast with stimulatory responses on different IGF-1 actions of the same binding protein reported previously [Elgin, Busby & Clemmons (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 3254-3258].
The cell decides... and I have always thought muscle injury and injury in general was an attracting event not a repelling event. I often mused about injecting IGF-1 bound to the IGF Binding Protein-3 which will bind to albumin in plasma into the injured/worked muscle. The size of this complex is too big to leave the area. It is too big to pass through the vessel walls and travel around systemically. It would sit at site and wait to be called to the injured/repairing cell... probably by factors that make travel through the matrix mortar that surrounds cells more easily traversed.
IGF-1 LR3 (altered IGF-1) and Des could not be used as they do not bind to the binding protein and would freely be taken up into the vessels blood streams.
Now des-(1-3)-IGF-1 has an increased potency BECAUSE it pretty much does not bind to binding proteins. It can not be pulled in when the cell wants nor easily repelled.
This increased potency was not associated with a comparable increase in affinity for the type 1 IGF receptor (Ballard et al., 1987, 1988). Instead, des-(1-3)-IGF-1 bound relatively poorly to proteins in media conditioned by the L6 myoblasts used for the bioassays (Bagley et al., 1989) and to a pure binding protein produced by MDBK cells (Szabo et al., 1988). We proposed that the higher potency of des-(1-3)-IGF- 1 was a result of increased concentrations of the free peptide being available for interaction with cell receptors (Szabo et al., 1988).
See that is how they are measuring potency. So in case you missed it, stated again,
The biological potencies of IGF-1, IGF-2 and des-(1-3)-IGF-I correlate inversely with their binding to proteins released into the medium by cells, so that the enhanced potency of des-(1-3)-IGF-1 is a consequence of it not binding to purified binding proteins or those released by cultured cells.
Des has a decreased affinity for the IGF receptor compared to the native ligand IGF-1. IGF-1 LR3 as well. So to be active they must be present in a high enough concentration and hope to bind to receptors where needed. However they are not discriminate.
Now studies in farm animals do show growth from IGF-1, IGF-1 LR3, Des and Insulin. Leaner tissue from the IGFs and more fat gain from insulin. So I am not saying IGFs have no growth value at high doses. I am simply mentioning how Des derives its potency and saying its activity is not targeted to an area.
.gif "IP Gear")
