Insulin and insulin-like growth factor I enhance regeneration in cultured adult rat sensory neurones

Abstract

Insulin and the insulin-like growth factors (IGFs) may directly affect the growth, development, and maintenance of the vertebrate nervous system. Previous in vitro studies have focused on embryonic nervous tissue. In this study the effects of insulin, IGF-I, IGF-II and nerve growth factor (NGF) on regeneration and neuronal survival were studied in cultured adult rat sensory neurones in a cell culture environment that limited non-neuronal cell mediated effects. Regeneration, as assessed by neurite outgrowth, was significantly enhanced by insulin and IGF-I in a dose-dependent manner. The half-maximally effective concentrations, ED50's, were approximately 1 nM and 0.1 nM for insulin and IGF-I, respectively. Concentrations of IGF-I as low as 10pM were active. There was some evidence that IGF-II stimulated regeneration, although this failed to reach statistical significance. NGF also promoted regeneration, confirming previous studies, exhibiting an ED50 of approximately 0.3 ng/ml and inducing a maximal response 2-fold greater than that observed with insulin or IGF-I. Combined treatment with NGF and insulin had an additive effect. Specific anti-NGF antiserum inhibited the regenerative response to NGF but failed to block the response to IGF-I, supporting the view that IGF-I was acting directly on sensory neurones rather than stimulating NGF production by non-neuronal cells. Insulin, IGF-I and NGF had no effect on neuronal survival in this culture system. These results show that adult sensory neurones can respond with enhanced regenerative growth to insulin and IGF-I, in addition to NGF although the response to IGF-II was less clear.