Insulin prevents depolarization of the mitochondrial inner membrane in sensory neurons of type 1 diabetic rats in the presence of sustained hyperglycemia

Mitochondrial dysfunction has been proposed as a mediator of neurodegeneration in diabetes complications. The aim of this study was to determine whether deficits in insulin-dependent neurotrophic support contributed to depolarization of the mitochondrial membrane in sensory neurons of streptozocin (STZ)-induced diabetic rats. Whole cell fluorescent video imaging using rhodamine 123 (R123) was used to monitor mitochondrial inner membrane potential (Δψ_m). Treatment of cultured dorsal root ganglia (DRG) sensory neurons from normal adult rats for up to 1 day with 50 mmol/l glucose had no effect; however, 1.0 nmol/l insulin increased Δψ_m by 100% (P < 0.05). To determine the role of insulin in vivo, STZ-induced diabetic animals were treated with background insulin and the Δψ_m of DRG sensory neurons was analyzed. Insulin therapy in STZ-induced diabetic rats had no effect on raised glycated hemoglobin or sciatic nerve polyol levels, confirming that hyperglycemia was unaffected. However, insulin treatment significantly normalized diabetes-induced deficits in sensory and motor nerve conduction velocity (P < 0.05). In acutely isolated DRG sensory neurons from insulin-treated STZ animals, the diabetes-related depolarization of the Δψ_m was corrected (P < 0.05). The results demonstrate that loss of insulin-dependent neurotrophic support may contribute to mitochondrial membrane depolarization in sensory neurons in diabetic neuropathy.