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 effects 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 proliferation in the outgrowth region. In nerves cultured for 11 days, a physiological dose (10 ng/ml, approximately 2 nM) of insulin or IGF-II increased ganglionic protein synthesis (by 20% and 50%, respectively) as well as the level of newly formed, radiolabelled axonal material distal to a crush injury (both by 80%), compared to untreated, paired controls. In addition, insulin increased the outgrowth distance of the furthest regenerating sensory axons by 10%. The preparation was particularly sensitive to insulin during the first 5 days of culturing. Furthermore, both insulin and IGF-II were found to inhibit proliferation of support cells in the outgrowth region in a manner suggesting effects via their individual receptors. The inhibition, about 30%, was observable after 4 but not 11 days in culture. It is not clear if this reflects 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 regulation of peripheral nerve regeneration.
Department of Animal Physiology, University of Lund, Sweden.
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Edbladh
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Fex-Svenningsen
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Ekström
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Edström
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016895:Culture Media, Serum-Free; D004247:DNA / Q000096:biosynthesis; D017950:Ganglia, Sensory / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D008360:Mannosephosphates / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D011896:Rana temporaria; D012584:Sciatic Nerve / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D016895:Culture Media, Serum-Free; D007328:Insulin; D008360:Mannosephosphates; D009419:Nerve Tissue Proteins; C027693:mannose-6-phosphate; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D004247:DNA