NEURON-LIKE PHENOTYPIC CHANGES IN PANCREATIC BETA-CELLS INDUCED BY NGF, FGF, AND DBCAMP

We studied the effects of nerve growth factor (NGF), fibroblast growth factor (FGF), and dibutyryl-cAMP (dbcAMP) on rat pancreatic beta-cell morphology and of NGF and dbcAMP on insulin secretion. After 2 wk in culture, nearly 3% of beta-cells extended neurite-like processes spont aneously; when cells were treated with NGF, almost 30% of them extende d processes. In the presence of dbcAMP, almost all beta-cells flattene d, and the extension of neurite-like processes was more pronounced in fetal than in adult cells. The most prominent effect, regardless of ag e, was observed in cells treated with NGF and dbcAMP together, since t he percentage of neurite-like bearing beta-cells increased to 50%. bet a-cells cultured under these conditions maintained their immunoreactiv ity to insulin and nearly all beta-cells and their neurite-like proces ses were also positive to GABA, tubulin, tau protein, and N-CAM. FGF i ncreased the percentage of adult beta-cells bearing neurite-like proce sses to 13%, and FGF and dbcAMP applied together to 40%. beta-cells tr eated with NGF and dbcAMP for 5 to 7 d preserved their capability to s ecrete the hormone in response to different extracellular glucose conc entrations. Insulin secretion of dbcAMP-treated beta-cells was 2.5-fol d higher than in control cells. NGF-treated cells were able to discrim inate between different glucose concentrations, a property lost in con trol cells with time in culture.