Development of diabetic neuropathy in the C57BL/Ks (db/db) mouse and its treatment with gangliosides.

We studied the development of diabetic neuropathy and its treatment with gangliosides using the C57BL/Ks mouse. The results of axonal morphometry showed the presence of a progressive axonal atrophy which was maximal at 180 days of age. To 400 days of age there was no longer any significant difference, perhaps due to aging processes. Nerve conduction velocity changed significantly from the early days of life. Thirty-day treatment with gangliosides significantly improved nerve conduction velocity and axonal morphometry at 180 and 280 days of life. No effect was observed with treatments at 30 or 60 days. It was previously shown that the early phase of the C57BL/Ks mouse neuropathy was reversed by insulin, whereas the late phase (180 days) was not. We showed elsewhere that at 180 days of age in the C57BL/Ks mouse there was a drastic decrease in slow transport of AChE (G1 and G2 molecular forms) indicating a shift in neuronal metabolism and suggesting that the disease was then more intrinsically neuronal. Using the suggestion of Robertson and Sima (Diabetes 29: 60-67, 1980) we label the first phase of the neuropathy "metabolic" (treatable with insulin) and the second phase "neuronal" (treatable with gangliosides). This "neuronal" phase could be related to the degenerative stage of human diabetic neuropathy.