Ablation of a small subpopulation of diabetes-specific

44 Diabetic peripheral neuropathy (DPN) is a major diabetic complication. We 45 previously showed that hyperglycemia induces the appearance of proinsulin 46 (PI)-producing bone marrow-derived cells (PI-BMDCs), which fuse with 47 dorsal root ganglion neurons, causing apoptosis, nerve dysfunction and DPN. 48 In this study, we have devised a strategy to ablate PI-BMDCs in mice in vivo. 49 Use of this strategy to selectively ablate TNF-α-producing PI-BMDCs in 50 diabetic mice protected these animals from developing DPN. The findings 51 provide powerful validation for a pathogenic role of PI-BMDCs, and identify 52 PI-BMDCs as an accessible therapeutic target for the treatment and 53 prevention of DPN. 54