Open AccessThe fusion of bone-marrow-derived proinsulin-expressing cells with nerve cells underlies diabetic neuropathy
Author(s) -
Tomoya Terashima,
Hideto Kojima,
Mineko Fujimiya,
Kazuhiro Matsumura,
Jiro Oi,
Manami Hara,
Atsunori Kashiwagi,
Hiroshi Kimurâ,
Hitoshi Yasuda,
Lawrence Chan
Publication year - 2005
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0505717102
Subject(s) - proinsulin , dorsal root ganglion , diabetic neuropathy , medicine , pathogenesis , bone marrow , diabetes mellitus , sciatic nerve , apoptosis , downregulation and upregulation , endocrinology , biology , dorsum , anatomy , gene , biochemistry
Diabetic neuropathy is the most common microvascular complication of diabetes. Here we show that, in streptozotocin-induced diabetic rodents with neuropathy, a subpopulation of bone-marrow-derived cells marked by proinsulin expression migrates to and fuses with neurons in the sciatic nerve and dorsal root ganglion (DRG), resulting in neuronal dysfunction and accelerated apoptosis. The absence or presence of proinsulin expression, which identifies the fusion cells, and not the disease state (nondiabetic vs. diabetic) of the rats from which the DRG neurons are isolated determines whether the DRG neurons show normal or abnormal calcium homeostasis and apoptosis. These results suggest that bone-marrow-derived cells may play an important role in the pathogenesis of diabetic complications.