Fine tuning of insulin secretion by release of nerve growth factor from mouse and human islet β-cells

Nerve growth factor (NGF) is a protein required for neuronal development that also has regulatory functions in non-neuronal cells. Both NGF and its membrane receptors trkA and p75^NTR are expressed by islet β-cells. In this study we dynamically profiled NGF secretion from islets and used selective trkA and p75^NTR inhibitors to identify the role of endogenous NGF in β-cell stimulus-secretion coupling. NGF secretion from mouse islets was transient and did not accompany the sustained second phase of glucose-induced insulin secretion. Despite being present in human islets, NGF was not released at sufficient levels to be quantified. Inhibition of NGF signaling through trkA and p75^NTR increased basal insulin secretion from both human and mouse islets, but impaired glucose-stimulated insulin secretion. These data support a role for islet NGF in fine-tuning insulin secretion, to both maintain a low basal level of insulin output and contribute to the biphasic secretory response to glucose.