Research Paper Volume 11, Issue 14 pp 4943—4969
D-ribose is elevated in T1DM patients and can be involved in the onset of encephalopathy
- 1 School of Basic Medical Sciences of Southwest Medical University, Luzhou 646000, China
- 2 State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, University of Chinese Academy of Sciences, Beijing 100101, China
- 3 Alzheimer’s Disease Center, Beijing Institute for Brain Disorders, Center for Brain Disorders Research, Capital Medical University, Beijing 100069, China
- 4 CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China
- 5 Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
Received: April 29, 2019 Accepted: July 4, 2019 Published: July 15, 2019
https://doi.org/10.18632/aging.102089How to Cite
Copyright © 2019 Yu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Although many mechanisms have been proposed for diabetic encephalopathy in type 2 diabetes mellitus (T2DM), the risk factors for cognitive impairment in type 1 diabetes mellitus (T1DM) are less clear. Here, we show that streptozotocin (STZ)-induced T1DM rats showed cognitive impairment in both Y maze and Morris water maze assays, accompanied with D-ribose was significantly increased in blood and urine, in addition to D-glucose. Furthermore, advanced glycation end products (AGE), Tau hyperphosphorylation and neuronal death in the hippocampal CA4/DG region were detected in T1DM rats. The expression and activity of transketolase (TKT), an important enzyme in the pentose shunt, were decreased in the brain, indicating that TKT may be involved in D-ribose metabolism in T1DM. Support for these change was demonstrated by the activation of TKT with benfotiamine (BTMP) treatment. Decreased D-ribose levels but not D-glucose levels; markedly reduced AGE accumulation, Tau hyperphosphorylation, and neuronal death; and improved cognitive ability in T1DM rats were shown after BTMP administration. In clinical investigation, T1DM patients had high D-ribose levels in both urine and serum. Our work suggests that D-ribose is involved in the cognitive impairment in T1DM and may provide a potentially novel target for treating diabetic encephalopathy.