Background: Diabetes mellitus is a metabolic disease which also causes cognitive deficits. Betaine (N,N,N-trimethylglycine), also known as trimethylglycine, has been shown to ameliorate diabetic symptoms in diabetic animals and improve cognitive ability in Alzheimer disease (AD) animals. However, the effects of betaine on cognitive deficits in diabetic animals have not been described yet. Therefore, in the current study, the effects of betaine on cognition in diabetic rats were evaluated. Methods: We established a diabetic rat model by injecting streptozotocin (STZ) into rats and administrated betaine to these diabetic rats. We monitored the metabolism index, and glucose and insulin levels in blood and cerebrospinal fluid. We measured inflammatory cytokine levels, including TNF-α, IL-1β, and IL-6, in serum and hippocampus. We also monitored oxidative stress in the hippocampus by measuring malondialdehyde (MDA) level and superoxide dismutase (SOD) activity. We measured the learning and memory ability of diabetic rats using the Morris water and Y maze tests and tested the phosphatidylinositol 3-kinase (PI3K)/Akt activation and p-mTOR level in the hippocampus. Results: Betaine improved glucose metabolism and suppressed the production of inflammatory cytokines, including TNF-α, IL-1β, and IL-6. Also, betaine decreased MDA concentration and increased SOD activity in the hippocampus of diabetic rats. Betaine ameliorated cognitive deficits in diabetic rats, and it promoted PI3K expression and Akt activation and decreased p-mTOR expression. Conclusion: Betaine alleviates cognitive deficits in STZ-induced diabetic rats via regulating the PI3K/Akt signaling pathway.
Dement Geriatr Cogn Disord

中文翻译：

---

甜菜碱通过PI3K / Akt信号通路调节减轻糖尿病大鼠的认知功能障碍。

背景：糖尿病是一种代谢性疾病，也会引起认知缺陷。甜菜碱（N，N，N-三甲基甘氨酸），也称为三甲基甘氨酸，已显示出改善糖尿病动物的糖尿病症状并改善阿尔茨海默病（AD）动物的认知能力。然而，尚未描述甜菜碱对糖尿病动物认知缺陷的影响。因此，在当前的研究中，评估了甜菜碱对糖尿病大鼠认知的影响。方法：我们通过向大鼠注射链脲佐菌素（STZ）并向这些糖尿病大鼠服用甜菜碱来建立糖尿病大鼠模型。我们监测了血液和脑脊液中的新陈代谢指数以及葡萄糖和胰岛素水平。我们测量了血清和海马中的炎性细胞因子水平，包括TNF-α，IL-1β和IL-6。我们还通过测量丙二醛（MDA）水平和超氧化物歧化酶（SOD）活性来监测海马的氧化应激。我们使用Morris水和Y迷宫测试测量了糖尿病大鼠的学习和记忆能力，并测试了海马中的磷脂酰肌醇3激酶（PI3K）/ Akt激活和p-mTOR水平。结果：甜菜碱可改善葡萄糖代谢并抑制包括TNF-α，IL-1β和IL-6在内的炎性细胞因子的产生。同样，甜菜碱可降低糖尿病大鼠海马中的MDA浓度并增加其SOD活性。甜菜碱改善了糖尿病大鼠的认知功能障碍，并促进了PI3K表达和Akt激活并降低了p-mTOR表达。结论：甜菜碱通过调节PI3K / Akt信号通路减轻STZ诱导的糖尿病大鼠的认知功能障碍。
Dement Geriatr Cogn Disord