A High-Carbohydrate Diet Induces Cognitive Impairment and Promotes Amyloid Burden and Tau Phosphorylation via PI3K/Akt/GSK-3β Pathway in db/db Mice

高碳水化合物饮食会诱发认知障碍,并通过 PI3K/Akt/GSK-3β 通路促进 db/db 小鼠的淀粉样蛋白负担和 Tau 磷酸化

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作者:Jialu Xu, Lei Xie, Jiaxin Yin, Xiaoli Shi, Kun Dong, Jing Tao, Weijie Xu, Delin Ma, Shujun Zhang, Juan Chen, Yan Yang

Background

Cognitive impairment is a prevalent complication of type 2 diabetes, influenced significantly by various dietary patterns. High-carbohydrate diets (HCDs) are commonly consumed nowadays; however, the specific impact of HCDs on cognitive function in diabetes remains unclear.

Conclusions

Collectively, our findings indicate that a high intake of carbohydrates can have an adverse impact on cognitive function in diabetes.

Methods

The objective of this study was to investigate whether an HCD has effects on cognition in diabetes. Eight-week-old diabetic (db/db) mice and wild-type (WT) mice underwent a twelve-week dietary intervention, including a normal diet (ND), an HCD, or a high-fat diet (HFD). Following this, behavioral tests were conducted, and related hippocampal pathology was evaluated.

Results

Our results demonstrated that an HCD exacerbated cognitive decline in db/db mice compared to an ND. Additionally, an HCD increased amyloid-β burden and expression of β-site APP cleaving enzyme-1. An HCD was also found to promote the phosphorylation of tau protein via the PI3K/Akt/GSK-3β pathway. Furthermore, an HCD markedly induced neuroinflammation and increased the quantity of microglia and astrocytes. However, these damages induced by an HCD were less severe than those caused by an HFD. Conclusions: Collectively, our findings indicate that a high intake of carbohydrates can have an adverse impact on cognitive function in diabetes.

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