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.
Highlights
Type 1 diabetes mellitus (T1DM) is a D-glucose metabolic disorder characterized by autoimmune destruction of pancreatic β-cells, leading to insulin deficiency and hyperglycaemia [1]
Rats were maintained for 10 weeks; during this period, their fasting blood glucose (FBG), body weight and forepaw tensions were monitored every other week (Supplementary Figure 1A–1C)
Representative images of the performance path of the rats are shown in Supplementary Figure 4E. These results indicated that type 1 diabetes mellitus (T1DM) rats exhibited cognitive impairment, which was regarded as type 1 diabetic encephalopathy
Summary
Type 1 diabetes mellitus (T1DM) is a D-glucose metabolic disorder characterized by autoimmune destruction of pancreatic β-cells, leading to insulin deficiency and hyperglycaemia [1]. T1DM can affect different organs and result in many complications; among these complications, diabetic encephalopathy is diabetesinduced brain damage [2]. As early as 1922, diabetes was recognized to lead to cognitive dysfunction [3]. Because an increasing number of people are diagnosed with T1DM or type 2 diabetes mellitus (T2DM), diabetic encephalopathy has become widely recognized [4,5,6]. Patients with diabetic encephalopathy show both mental and physical symptoms, including an altered mental state, cognitive decline, memory lapses, and changes in personality [2, 7]. Compared with people without diabetes mellitus, people with diabetes are at higher risk www.aging-us.com of cognitive decline and dementia, such as Alzheimer's disease [8]
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