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.