Aldose Reductase‐Deficient Mice Are Protected From Reduction Of Nerve Conduction Associated With Diabetes

Abstract

Previously, we have shown that aldose reductase (AR) mRNA is strongly expressed by Schwann cells and not expressed by the endothelial cells in the sciatic nerve. Additional over‐expression of AR in the Schwann cells lead to further reduction of motor nerve conduction velocity (MNCV) in diabetic and more prominently in galactosemic mice, suggesting AR's contribution to hyperglycemic and galactosemic lesions in the nerve. Here, we report the deletion of AR gene in mice to study its physiological functions and to understand its role in the pathogenesis of diabetic neuropathy. The homozygous AR‐deficient mice showed no apparent developmental or reproductive abnormalities except they drink and urinate significantly more than their wildtype littermates due to a partially defective urinary concentrating ability. These AR knockout mice are then converted to become diabetic by streptozotocin (STZ) treatment to determine the effects of AR‐deficiency on the MNCV. The diabetic mice, whether they are AR deficient or wildtype mice, drank and urinated similarly. Whereas the wildtype showed significant reduction in MNCV after 4 weeks of STZ treatment (p < 0.01), the AR‐deficient mice did not show any significant reduction in MNCV. Interestingly, the AR‐deficient mice have less body weight reduction after 4 weeks of diabetes compared to those of wildtype mice treated to STZ (p < 0.05) suggesting that AR deficiency has an overall beneficial effect on diabetic mice.