Islet Cell Transplantation Prevents Myelinated Nerve Fibre Pathology in the C57BL/6-Ins2Akita Mouse.

The C57BL/6-Ins2Akita mouse (B6-Akita) is a model of spontaneous early-onset diabetes mellitus, characterized by a reduced number of pancreatic beta cells expressing a mutant non-functional isoform of insulin. B6-Akitas are characterized by hypoinsulinemia and hyperglycemia. We have assessed nerve function and structure to determine if Akita mice were a suitable model for the study of diabetic neuropathy. Foot sensory nerve amplitudes and motor nerve conduction velocity were significantly reduced in 6 month old diabetic Akita compared to age matched Ins2+/+ control mice (p<0.05). These results demonstrate that B6-Akita mice exhibit impaired peripheral nerve function. To determine if islet transplantation would reverse the neurological defects we examined sensory nerve morphology comparing in 7 week old B6-Akita mice which had undergone syngeneic pancreatic islet transplantation (Akita+PIT) ∼100 days prior to saphenons nerve biopsy with age matched non-islet transplanted B6-Akitas (n=3). Blood glucose levels, taken weekly were significantly reduced in Akita+PIT group. Akita+PIT mice had glucose levels <200mg/dL, 1 wk after engraftment with islets. In comparison, non-transplanted mice always exhibited blood glucose levels >500mg/dL. There was no significant difference in: Fascicular area (Akita+PIT (0.15 ± 0.04) v Akita 0.05 ± 0.01), p=0.136); myelinated nerve fibre density (no.mm-2) (Akita+PIT (20206 ± 1360) vs. Akita (21244 ± 2012), p=-0.633) or endoneurial capillary density (no.mm-2) (Akita+PIT (68.5 ± 10.2) v Akita (68.2 ± 11.0), p=l.0). However, detailed electroumicroscopy of the myelinated fibres demonstrated that islet transplantation protected against a reduction in myelinated fibre (Akita+PIT (32.2 ± 4.5) v Akita (22.3 ± 5.2) p=0.07) and axon (Akita+PIT (12.4±1.9) v Akita (7.8 ± 3.2) p=-0.07) areas (µm2); without a change in the G ratio (Akita+PIT (0.61 ± 0.06) v Akita (0.57 ± 0.04) p=0.29). In conclusion B6-Akita mice demonstrate significant reductions in nerve function and structural abnormalities include a reduction of myelinated fibre and axon area which is prevented by pancreatic islet transplantation. [ABSTRACT FROM AUTHOR]