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

Abstract

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.

Keywords: Insulin secretion; Islets of Langerhans; NGF; p75(NTR); trkA; β-cells.