Impaired neuronal mitochondrial bioenergetics contributes to the progression of diabetic peripheral neuropathy (DPN). We have demonstrated that modulating heat shock protein 90 (Hsp90) and Hsp70 with KU-32 ameliorates deficits of DPN in animal models of type 1 diabetes. The current study used mouse models of types 1 and 2 diabetes to determine the relationship of changes in sensory neuron mitochondrial bioenergetics to the onset of and recovery from DPN. KU-32 therapy improved mitochondrial bioenergetics in both the type 1 and type 2 models, and this tightly correlated with a decrease in DPN. Mechanistically, improved mitochondrial function following KU-32 therapy required Hsp70 because the drug was ineffective in diabetic Hsp70 knockout mice. Our data indicate that changes in mitochondrial bioenergetics may rapidly contribute to nerve dysfunction in type 2 diabetes but not type 1 diabetes and that modulating Hsp70 offers an effective approach toward correcting sensory neuron bioenergetics deficits.
See article at J Pharmacol Exp Ther 2014, 348:281–292.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics