Effects of insulin-like growth factors on protein metabolism: why are some molecular variants more potent?
The insulin-like growth factors (IGFs) produce a dual anabolic effect on protein metabolism in cultured cells via a stimulus of the synthetic pathway and an inhibition of the degradative pathway. Accordingly, they offer promise as agents that may retard the extensive and life-threatening negative nitrogen balance that accompanies human polytrauma. In this report we describe the discovery of a novel, more potent, form of IGF-1, des-(1-3)-IGF-1, and explain its increased action as resulting from higher concentrations of the free peptide produced because des-(1-3)-IGF-1 binds very poorly to IGF carrier proteins released from most cell types. The truncated growth factor retains a long biological half-life because it is attached to blood IGF-binding proteins. Further understanding of the biological significance of IGF, coupled with synthetic approaches directed at the production of mutant IGF-1 molecules, can be expected to yield significant advances in the treatment of polytrauma.
Ballard
F J
FJ
CSIRO Division of Human Nutrition, University of Adelaide, Australia.
Francis
G L
GL
Bagley
C J
CJ
Szabo
L
L
Wallace
J C
JC
D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002642:Chick Embryo; D006207:Half-Life; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000378:metabolism*
D002352:Carrier Proteins; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; C058957:insulin-like growth factor 1, des-(1-3)-; D007334:Insulin-Like Growth Factor I