Degenerative neuropathy in insulin-treated diabetic rats

Peripheral neuropathic alterations associated with diabetes and its treatment with insulin were studied in alloxan-induced diabetic rats. Treatment regimens included daily injections of Protamine Zinc Insulin (PZ), daily injections of Ultralente Insulin and subcutaneously implanted osmotic minipump delivered insulin. Non-diabetic and untreated diabetic groups served as controls. Two separate but similar studies were run, one lasting 4 weeks and the other 8 weeks. Conduction velocities performed on both sensory and motor nerves revealed no statistically significant differences among groups. Anatomical analysis of teased fibers from tibial nerves showed a significant number of fibers with ovoids, consistent with Wallerian-type axonal degeneration, only in the treated diabetic groups. Degeneration was especially severe in the PZI-treated group. Metabolic studies were performed using incorporation of radioactive isotopes ([3H]fucose, [14C]leucine) into myelin proteins of sciatic nerves. The ratio of [3H]fucose/[14C]leucine for the PZI-treated group was significantly decreased when compared to the control groups in both the 4 and 8 week study whereas the minipump-treated group showed no statistically significant difference from the control group in either study. Similar decreases in this ratio have been seen in conditions of peripheral nerve degeneration. It is concluded that daily injections of PZI insulin result in significant nerve degeneration in the alloxan diabetic rat, while continuous levels of insulin delivered by osmotic minipumps result in less degeneration.