Download This Paper
Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.
D-Ribose Plays a Crucial Role in Type 1 Diabetic Encephalopathy
40 Pages Posted: 28 Mar 2019
More...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).
Keywords: D-ribose, benfotiamine (BTMP), cognitive impairment, type 1 diabetic encephalopathy, type 1 diabetes mellitus (T1DM), diabetic encephalopathy
Suggested Citation: Suggested Citation