D-Ribose Plays a Crucial Role in Type 1 Diabetic Encephalopathy

Abstract

Diabetic encephalopathy is the brain damage caused by diabetes mellitus and has been recognized and diagnosed in both type 1 and type 2 diabetes mellitus (T1DM and T2DM, respectively). Although many mechanisms have been proposed for diabetic encephalopathy in type 2 diabetes mellitus, the risk factors for cognitive impairment in T1DM are less clear. Here, T1DM patients had abnormally high D-ribose levels in both urine and serum. In streptozotocin-induced T1DM rats, blood and urine D-ribose levels were also significantly increased, accompanied by spatial cognitive impairment in Y maze and Morris water maze assays. Furthermore, advanced glycation end product (AGE) formation, Tau hyperphosphorylation and neuronal death in the hippocampal CA4/DG region were detected in T1DM rats. The expression and activity of transketolase, an important enzyme in the pentose shunt, were decreased, indicating that transketolase may control D-ribose metabolism in T1DM. This assumption was confirmed by the activation of transketolase with benfotiamine. Decreased D-ribose levels; reduced AGE accumulation, Tau hyperphosphorylation, and neuronal death; and improved cognitive ability in T1DM rats were shown after benfotiamine administration. Our work suggests that D-ribose plays a crucial role in the cognitive impairment in T1DM and may provide a novel target for treating diabetic encephalopathy. Funding: This work was supported by grants from Natural Scientific Foundation of China NSFC (31670805), National Key Research and Development Program of China (2016YFC1305900; 2016YFC1306300), Beijing Municipal Science and Technology Project (Z161100000217141 and Z161100000216137), and Youth Innovation Promotion Association CAS (2017132). Declaration of Interest: All authors declared no competing interests in this study. Ethical Approval: The handling of rats and experimental procedures have been approved by the Animal Welfare and Research Ethics Committee of the Institute of Biophysics, Chinese Academy of Sciences (Permit Number: SYXK2016-32).