设为首页 |  加入收藏 |  联系我们

如:神经外科 骨科 手外科 眼科 神经内科……

Neurotrophin Signaling Is Required for Glucose-Induced Insulin Secretion.

发布日期:2017-01-03 点击次数:1552 字体显示:【大】  【中】  【小】

Neurotrophin Signaling Is Required for Glucose-Induced Insulin Secretion.

【Author】 Houtz JBorden PCeasrine AMinichiello LKuruvilla R

 

【Author information】

Department of Biology, Johns Hopkins University, 3400 North Charles Street, 224 Mudd Hall, Baltimore, MD 21218, USA.

Department of Pharmacology, University of Oxford, OX1 3QT Oxford, UK.

Department of Biology, Johns Hopkins University, 3400 North Charles Street, 224 Mudd Hall, Baltimore, MD 21218, USA. Electronic address: rkuruvilla@jhu.edu.

 

【Abstract】

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.

DOI: 10.1016/j.devcel.2016.10.003