Diabetic neuropathy in the mutant mouse [C57BL/ks(db/db)]: a morphometric study.

Detailed studies of peripheral nerves were undertaken in the mutant diabetic mouse of the [C57BL/ks(db/db)] strain using electrophysiologic and morphometric techniques. Electrophysiologic studies showed severely impaired motor nerve conduction velocity (MNCV), which developed promptly during the early phase of the diabetic syndrome. Morphometric changes occurred first after 20 wk of diabetes in both myelinated and unmyelinated fibers. There were both loss and shrinkage of myelinated fibers, most pronounced in the sural nerve and the ventral root. Changes appeared late in the dorsal root and in the peroneal and vagus nerves. Unmyelinated fibers showed both shrinkage and loss of axons, presumably involving sympathetic and afferent somatic fibers. Teased fiber studies and calculations of axon-myelin ratios confirmed our earlier suggestion that the neuropathy is primarily axonal in nature. The temporal discrepancy between functional and structural impairments in the present model strongly suggests a metabolic cause of the early neuropathy. This was further supported by the positive effect of insulin treatment on MNCV during the early phase of diabetes, whereas, during the late phase, treatment failed to show any effect.