| First Author | Houtz J | Year | 2016 |
| Journal | Dev Cell | Volume | 39 |
| Issue | 3 | Pages | 329-345 |
| PubMed ID | 27825441 | Mgi Jnum | J:237506 |
| Mgi Id | MGI:5812833 | Doi | 10.1016/j.devcel.2016.10.003 |
| Citation | Houtz J, et al. (2016) Neurotrophin Signaling Is Required for Glucose-Induced Insulin Secretion. Dev Cell 39(3):329-345 |
| abstractText | Insulin secretion by pancreatic islet beta cells is critical for glucose homeostasis, and a blunted beta 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 beta 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 beta cell dysfunction. |
