The Fusion of Bone-Marrow-Derived Proinsulin-Expressing Cells with Nerve Cells Underlies Diabetic Neuropathy

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 dorsa...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2005-08, Vol.102 (35), p.12525-12530
Main Authors: Terashima, Tomoya, Kojima, Hideto, Fujimiya, Mineko, Matsumura, Kazuhiro, Oi, Jiro, Hara, Manami, Kashiwagi, Atsunori, Kimura, Hiroshi, Yasuda, Hitoshi, Chan, Lawrence, Wakil, Salih J.
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Biological Sciences
Bone marrow cells
Bone Marrow Cells - metabolism
Bone Marrow Transplantation
Calcium - metabolism
Cell Fusion
Cells, Cultured
Diabetes
Diabetes complications
Diabetes Mellitus, Experimental - complications
Diabetic neuropathies
Diabetic Neuropathies - etiology
Diabetic Neuropathies - genetics
Diabetic Neuropathies - metabolism
Diabetic Neuropathies - pathology
Ganglia, Spinal - metabolism
Ganglia, Spinal - pathology
Gene Expression
Homeostasis
In Situ Hybridization
Messenger RNA
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neurons
Neurons - metabolism
Polyploidy
Proinsulin - biosynthesis
Proinsulin - genetics
Rats
Rats, Sprague-Dawley
RNA, Messenger - genetics
RNA, Messenger - metabolism
Schwann cells
Sciatic nerve
Sciatic Nerve - metabolism
Sciatic Nerve - pathology
Transplantation, Homologous
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0505717102