Peripheral neuropathy in the WBN/Kob rat with chronic pancreatitis and spontaneous diabetes

To elucidate the mechanisms of peripheral nerve damage in diabetic neuropathy, various animal models have been studied. The WBN/Kob rat is a new animal model that develops chronic pancreatitis and spontaneous diabetes. It remains unestablished whether spontaneously diabetic rats of this strain develop peripheral neuropathy, comparable to the human diabetic neuropathy.

In the present study, we examined electrophysiologic, biochemical, and structural changes of peripheral nerve in 12- and 20-month-old diabetic WBN/Kob rats.

All the WBN/Kob rats showed slowing of motor nerve conduction and temporal dispersion of compound muscle action potential. Biochemical measurement revealed increased sorbitol and decreased myoinositol levels in the sciatic nerve. Structurally, de- and remyelination was the major abnormality in the sciatic and tibial nerves in 12-month-old rats. Twenty-month-old rats showed in addition, structural changes indicative of axonal degeneration and dystrophy. Morphometric analysis demonstrated reduced myelinated fiber occupancy and decreased mean myelinated fiber size. These structural changes appeared to be the most conspicuous around the endoneurial vessels. They were less severe in the sural nerve.

The WBN/Kob rat develops demyelinating, predominantly motor neuropathy, later accompanied by axonal changes. The neuropathic manifestations are unique as compared with those found in other spontaneously diabetic animal models. Late appearing axonal changes may correlate to diabetic dysmetabolism but the mechanism of early demyelination remains to be determined.