Implication of nitric oxide in NGF-induced cell differentiation: differences between neuronal and beta cells.

Both pancreatic beta cells (insulin-secreting cells) and neuronal cells express functional receptors for nerve growth factor. However, while the effect of nerve growth factor on neuronal differentiation is well known, its role on pancreatic beta cells is not established. It has been demonstrated that in PC12 cells, a well characterized NGF-responsive cell line, NGF increases the production of nitric oxide by inducing the expression of nitric oxide synthase. Nitric oxide is subsequently responsible for growth arrest, a step necessary for neuronal differentiation, visualized by the extension of neuronal-like processes. In the present study, we studied the effect of nerve growth factor on nitric oxide synthesis in INS-1 cells, an insulin-producing cell line which possesses the machinery necessary to respond to nerve growth factor. It was demonstrated that the expression of none of the three isoforms of nitric oxide was induced by nerve growth factor in INS-1 cells, strongly suggesting that nerve growth factor does not induce an increase in nitric oxide production in this cell line. Finally, we demonstrated that whereas growth arrest occurred in INS-1 cells cultured in the presence of a donor of nitric oxide (SNP), the simultaneous addition of SNP and nerve growth factor is not sufficient to induce the extension of neuronal-like processes in INS-1 cells. These dissimilarities strongly suggest that NGF plays a different role in neuronal and pancreatic beta cells.