NERVE GROWTH-FACTOR INDUCES NEURON-LIKE DIFFERENTIATION OF AN INSULIN-SECRETING PANCREATIC BETA-CELL LINE

Nerve growth factor (NGF) is the best understood of a class of trophic proteins that are important for the survival of neurons and the elaboration of their characteristic processes. Here we demonstrate that RINm5F, a rat insulinoma cell line representing an early stage in pancreatic beta cell differentiation, expresses both the Trk and p75 NGF receptors and responds to NGF by extending neurite-like (neurofilament-containing) processes. NGF treatment of RINm5F cells also induces the expression of genes normally responsive to NGF in neurons, including the NGF-1A gene. Inasmuch as pancreatic beta cells arise from the embryonic endoderm, these results suggest that NGF may play a wider role during development than previously thought-a role not restricted to cells of neuroectodermal origin-and that endocrine and neuronal cells share a developmental pathway. The specific effect of NGF on an early pancreatic beta cell line also suggests that this neurotrophic factor might form the basis of a therapeutic treatment for some types of diabetes by inducing the proliferative differentiation of islet cells.