Abstract
Although recent studies have revealed that biochemical changes caused by hyperglycemia in diabetic nerves might play an important role in the development of diabetic neuropathy, the exact relationship between these changes and acute or chronic electrophysiologic changes of peripheral nerves has not been definitely established.
In this study, the importance of sorbitol accumulation in the nerve tissue in relation to the development of nerve dysfunction was investigated using a newly developed inhibitor of aldose reductase, a rate-limiting enzyme of the polyol pathway. The sorbitol content of the nervous tissue increased significantly when hyperglycemia developed in streptozotocin diabetic rats. The impairment of motor nerve conduction velocity (MNCV) appeared when the sorbitol content reached a certain threshold level.
The administrtion of aldose reductase inhibitor (ARI) immediately after streptozotocin injection prevented the reduction of MNCV, whereas the sorbitol content of nerve tissue increased above normal range, which suggested that neurophysiological function might be preserved if the accumulation of sorbitol remained less than a threshold level.
ARI tretment restored the decreased MNCV in streptozotocin diabetic rats and significantly reduced the sorbitol content of nerve tissue.
These results suggested that the sorbitol content of nerve tissue contributes to the development of nerve dysfunction in the acute diabetic state, and that ARI, by reducing sorbitol accumulation, is beneficial in the treatment of diabetic neuropathy.
