INSULIN AND IGF-II, BUT NOT IGF-I, STIMULATE THE IN-VITRO REGENERATION OF ADULT FROG SCIATIC SENSORY AXONS

We used the in vitro regenerating frog sciatic nerve to look for effec ts of insulin and insulin-like growth factors I and II (IGF-I, IGF-II) on regeneration of sensory axons and on injury induced support cell p roliferation in the outgrowth region. In nerves cultured for 11 days, a physiological dose (10 ng/ml, almost-equal-to 2 nM) of insulin or IG F-II increased ganglionic protein synthesis (by 20% and 50%, respectiv ely) as well as the level of newly formed, radiolabelled axonal materi al distal to a crush injury (both by 80%), compared to untreated, pair ed controls. In addition, insulin increased the outgrowth distance of the furthest regenerating sensory axons by 10%. The preparation was pa rticularly sensitive to insulin during the first 5 days of culturing. Furthermore, both insulin and IGF-II were found to inhibit proliferati on of support cells in the outgrowth region in a manner suggesting eff ects via their individual receptors. The inhibition, about 30%, was ob servable after 4 but not 11 days in culture. It is not clear if this r eflects a stimulated differentiation of some cells. By contrast, IGF-I lacked effects on both regeneration and proliferation. In conclusion, the results suggest that insulin and IGF-II are involved in the regul ation of peripheral nerve regeneration.