Nerve growth factor increases insulin secretion and barium current in pancreatic beta-cells

We analyzed the effect of a brief exposure to nerve growth factor (NGF) on insulin secretion and macroscopic barium currents of single adult rat pancr eatic P-cells. After a 1-h exposure to NGF (50 ng/ml), single P-cells show a 2.5-fold increase in the insulin secretion index in 5.6 mmol/l glucose an d a nearly twofold increase in 15.6 mmol/l glucose compared with control ce lls. We have recently demonstrated that pancreatic P-cells synthesize and s ecrete NGF. We analyzed the effect of endogenous NGF on insulin secretion b y incubating islet cells in the presence of an anti-NGF monoclonal antibody for 1 h in different glucose concentrations. Although the basal insulin se cretion index (5.6 mmol/l glucose) is not affected, glucose-stimulated insu lin secretion (15.6 mmol/l glucose) is decreased by 41% in the presence of the antibody. This effect is mediated by the activation of the NGF receptor TrkA because the specific inhibitor of Trk phosphorylation K252a also bloc ks NGF-induced increase in insulin secretion, both in the presence and abse nce of exogenous NGF. Using the whole-cell variation of the patch-clamp tec hnique, we found that cells exposed to NGF for 5 min exhibit a 32% increase in the average barium current density. These results suggest that the effe cts of NGF on insulin secretion are partially mediated by an increase in ca lcium current through Ca channels. These results further suggest that NGF p lays an important autoregulatory role in pancreatic P-cell function. Two ta rgets of short-term NGF-modulation are insulin secretion and calcium-channe l activity.