Time‐dependent effects of insulin on Schwann cell proliferation in the in vitro regenerating adult frog sciatic nerve

The present study showed that insulin (0.01 μg/ml, ≈︂ 2 nM) inhibited [³H]‐thymidine incorporation in support cells, most likely Schwann cells, of the cultured frog sciatic nerve. A 25–35% inhibition took place in regenerating nerve preparations as well as in preparations devoid of neuronal protein synthesis, i.e., in isolated 5 mm nerve segments and in gangliectomized nerves, suggesting that the effect was direct and not mediated via the neuronal cells. The inhibition by insulin was time‐dependent in that an effect was seen after 4 days but not at shorter or at longer periods of culturing. In separate experiments biotinylated insulin was shown to be taken up by Schwann cells in the regenerating nerve. Addition of serum increased the [³H]‐thymidine incorporation severalfold and abolished the inhibitory action of insulin. Our results suggest that insulin, at a certain stage of the regeneration programme, exerts a direct, inhibitory effect on the proliferation of the Schwann cells in the cultured frog sciatic nerve. © 1993 Wiley‐Liss, Inc.