NEAR NERVE LOCAL INSULIN PREVENTS CONDUCTION SLOWING IN EXPERIMENTAL DIABETES

Insulin may have direct effects on axons through its actions on insuli n receptors or through cross occupancy of insulin-like growth factor-1 receptors. We tested the hypothesis that insulin itself influences co nduction of myelinated fibers independent of hyperglycemia in experime ntal diabetes. Low dose intermittent (0.2 units thrice weekly) Toronto (regular) insulin was injected at the sciatic notch and knee near the left sciatic nerve of rats rendered diabetic with citrate buffered st reptozotocin or nondiabetic rats given citrate only. Identical volumes of normal saline were injected near the contralateral right sciatic n erve. The diabetic rats developed hyperglycemia, elevated glycosylated hemoglobin levels and had slowing of right (saline treated) sciatic t ibial motor and caudal sensory conduction velocity. In contrast, local insulin treatment on the left side prevented conduction slowing, unil aterally increasing conduction velocity. In nondiabetic rats, conducti on velocities were slightly higher on the insulin treated side, but th e influence of insulin was less robust than in diabetics. The insulin treated sural branches of the sciatic nerves in diabetics had a higher percentage of small (less than or equal to 9.0 mu m diameter) myelina ted fibers than the saline treated nerves. Local insulin has a trophic influence on myelinated fibers that is prominent in diabetic nerves a nd is independent of hyperglycemia. (C) 1997 Elsevier Science B.V.