Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Insulin secretion by pancreatic islet β cells is critical for glucose homeostasis, and a blunted β cell secretory response is an early deficit in type 2 diabetes. Here, we uncover a regulatory mechanism by which glucose recruits vascular-derived neurotrophins to control insulin secretion. Nerve growth factor (NGF), a classical trophic factor for nerve cells, is expressed in pancreatic vasculature while its TrkA receptor is localized to islet β cells. High glucose rapidly enhances NGF secretion and increases TrkA phosphorylation in mouse and human islets. Tissue-specific deletion of NGF or TrkA, or acute disruption of TrkA signaling, impairs glucose tolerance and insulin secretion in mice. We show that internalized TrkA receptors promote insulin granule exocytosis via F-actin reorganization. Furthermore, NGF treatment augments glucose-induced insulin secretion in human islets. These findings reveal a non-neuronal role for neurotrophins and identify a new regulatory pathway in insulin secretion that can be targeted to ameliorate β cell dysfunction.

Original publication




Journal article


Dev Cell

Publication Date





329 - 345


actin remodeling, endosomal signaling, glucose homeostasis, human islets, insulin secretion, neurotrophins, pancreatic vasculature, pericytes, Actins, Animals, Endocytosis, Exocytosis, Gene Deletion, Glucose, Glucose Intolerance, Glucose Tolerance Test, Homeostasis, Humans, Insulin, Integrases, Mice, Inbred C57BL, Models, Biological, Nerve Growth Factor, Organ Specificity, Pancreas, Phosphorylation, Receptor, trkA, Signal Transduction