Beneficial Effect of Org 2766 in Treatment of Peripheral Neuropathy in Streptozocin-Induced Diabetic Rats

Abstract

An injection of streptozocin (STZ) was used to study diabetes-induced peripheral neuropathy inrats. In such rats the values of motor nerve conduction velocity and sensory nerve conduction velocity were decreased compared with the values obtained in nondiabetic controls from 3 wk after STZ injection onward. In recent years it has been extensively documented that peptides related to ACTHand MSH exert a neurotrophic effect on the nervous system that results in enhanced recovery of function after mechanical nerve damage. This article documents the beneficial effect of the peptide Org 2766, an ACTH-(4–9) analogue, in diabetic peripheral neuropathy. Chronic subcutaneous treatmentof diabetic rats with Org 2766 results in a significant enhancement of both motor and sensory nerve conduction velocity compared with saline-treated diabetic rats. Histological analysis of cross sections of the sural nerve showed no difference in the total number of nerve fibers in saline- or peptide-treated diabetic rats. In contrast, a difference in fiber size distribution was demonstrated; i.e., the sural nerves of diabetic rats contained fewer thick myelinated fibers. Treatment with Org 2766 resulted in a normal distribution. Apparently, the peptide Org 2766 has a protective action on nerve fibers and nerve function during STZ-induced diabetes.