Fig. 4.

The role of neurotrophin receptors and their activators in either maintaining (a) or pruning (b) islet sympathetic nerves (ISNs). In the non-diabetic state (a), normal sympathetic innervation of the islet is maintained by a balance between an axonal maintenance signal (+), provided by NGF stimulation of tropomyosin receptor kinase A (Trk A) receptors, and an axonal pruning signal (−), provided by BDNF stimulation of the p75^NTR. During an immune attack on the islet (b), an increase in either islet BDNF or islet ROS increases activation of the p75^NTR. Simultaneously, a decrease in beta cell-derived NGF reduces the stimulation of Trk A receptors. Together, there is a dramatic shift of the balance toward axonal pruning (dashed lines)