Insulin and the insulin-like growth factors I and II are mitogenic to cultured rat sciatic nerve segments and stimulate [3H]thymidine incorporation through their respective receptors.
The factors that control proliferation of Schwann cells during peripheral nerve regeneration are not yet known. In this study we investigated the effects of insulin, insulin-like growth factor I and II (IGF-I and IGF-II), IGF-I analogues, and factors that interfere with their respective receptors, on [3H]thymidine incorporation into cultured nerve segments from the rat sciatic nerve. Segments cultured in nM (0.1-1.7 nM) concentrations of insulin, truncated IGF-I (tIGF-I), long R3IGF-I, or IGF-II exhibited an increase in [3H]thymidine incorporation compared with control segments. IGF-II was most potent. JB1, an IGF-I antagonist, counteracted the effects of tIGF-I and insulin. The results suggest that non-neuronal cells in the nerve segment, probably Schwann cells, possess distinct receptors for insulin, IGF-I, and IGF-II and that these receptors may be involved in the control of Schwann cell proliferation during peripheral nerve regeneration.
Department of Animal Physiology, University of Lund, Sweden.
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Fex Svenningsen
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Kanje
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D008024:Ligands; D008360:Mannosephosphates / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D017527:Receptor, IGF Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism; D012584:Sciatic Nerve / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013268:Stimulation, Chemical; D013936:Thymidine / Q000378:metabolism*
D007004:Hypoglycemic Agents; D007328:Insulin; D008024:Ligands; D008360:Mannosephosphates; D008934:Mitogens; D017527:Receptor, IGF Type 2; C027693:mannose-6-phosphate; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D013936:Thymidine