Author(s)

Sergey Lupachyk, Hanna Shevalye, Pierre Watcho, Alexander Obrosov, Irina G. Obrosova, Mark A. Yorek

Department of Veterans Affairs Iowa City Health Care System and Department of Internal Medicine, University of Iowa, Iowa City, USA.
Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, USA.

To determine the effect of Na+/H+-exchanger-1 on diabetic neuropathy in Type 2 diabetes Zucker diabetic fatty (ZDF) rats and lean controls were treated with cariporide (10 or 20 mg/kg/d), a Na+/H+-exchanger-1 inhibitor, for 4 weeks at 15 weeks of age. Neuropathy endpoints included motor (MNCV) and sensory (SNCV) nerve conduction velocities, thermal nociception, tactile allodynia and intraepidermal nerve fiber density. Advanced glycation endproduct and markers of oxidative stress including nitrated protein levels in sciatic nerve and dorsal root ganglion were also evaluated. Expression of Na+/H+-exchanger-1 in dorsal root ganglion neurons was increased in ZDF rats. At 15 weeks of age ZDF rats displayed hyperglycemia, MNCV and SNCV deficits, thermal hypoalgesia and tactile allodynia. At 20 but not 10 mg/kg/d, cariporide significantly improved MNCV and SNCV deficits, thermal hypoalgesia and tactile allodynia. Cariporide treatment was also associated with reduction of diabetes-induced accumulation of advanced glycation end-product (AGE), oxidative stress and nitrated proteins in sciatic nerve and dorsal root ganglion neurons. In conclusion, these findings support an important role for Na+/H+-exchanger-1 in peripheral diabetic neuropathy, and provide rationale for development of Na+/H+-exchanger-1 inhibitors for treatment of diabetic neural complications.

Diabetic Neuropathy; Sodium/Hydrogen Exchanges; Oxidative Stress

Lupachyk, S. , Shevalye, H. , Watcho, P. , Obrosov, A. , Obrosova, I. and Yorek, M. (2014) Treatment of peripheral diabetic neuropathy in Zucker diabetic fatty (ZDF) rats with cariporide. Journal of Diabetes Mellitus, 4, 59-66. doi: 10.4236/jdm.2014.41011.