Reversible and irreversible nodal dysfunction in diabetic neuropathy

Abstract

Acute reversible diabetic nerve dysfunction has been associated with a reversible myo‐inositol–related (Na⁺ + K⁺)‐ATPase defect, while poorly reversible chronic nerve dysfunction correlates with progressive axoglial dysjunction of peripheral nerve. The causal relationships between biochemical and neuroanatomical abnormalities and those of nodal membrane function are not known. Nodal clamp examinations were carried out in the sciatic nerve of diabetic BB‐rats to elucidate the events underlying diabetic nerve dysfunctions and how these relate to metabolic and structural defects of diabetic nerve. With increasing duration of diabetes, there was a progressive decline in nodal action potentials attributable to decreased Na⁺ permeability and a decrease in the membranous Na⁺ gradient. Vigorous insulin therapy in short‐term (6‐week) diabetic BB‐rats normalized the Na⁺‐permeability defect and the membranous Na⁺ gradient. These defects did not reverse in long‐term (24‐week) diabetic animals subjected to the same treatment. This poorly reversible nodal dysfunction accounts for the not readily reversible conduction defect in chronic diabetes and is probably directly related to irreversible axoglial dysjunction.