AIMS Exposure to recurrent hypoglycemia (RH) is common in diabetic patients receiving glucose-lowering therapies and is implicated in causing cognitive impairments. Despite the significant effect of RH on hippocampal function, the underlying mechanisms are currently unknown. Our goal was to determine the effect of RH exposure on hippocampal metabolism in treated streptozotocin-diabetic rats. METHODS Hyperglycemia was corrected by insulin pellet implantation. Insulin-treated diabetic (ITD) rats were exposed to mild/moderate RH once a day for 5 consecutive days. RESULTS The effect of RH on hippocampal metabolism revealed 65 significantly altered metabolites in the RH group compared with controls. Several significant differences in metabolite levels belonging to major pathways (eg, Krebs cycle, gluconeogenesis, and amino acid metabolism) were discovered in RH-exposed ITD rats when compared to a control group. Key glycolytic enzymes including hexokinase, phosphofructokinase, and pyruvate kinase were affected by RH exposure. CONCLUSION Our results demonstrate that the exposure to RH leads to metabolomics alterations in the hippocampus of insulin-treated streptozotocin-diabetic rats. Understanding how RH affects hippocampal metabolism may help attenuate the adverse effects of RH on hippocampal functions.

中文翻译：

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暴露于反复低血糖会改变经治疗的链脲佐菌素诱导的糖尿病大鼠的海马代谢。

目的 接受降糖治疗的糖尿病患者经常出现复发性低血糖 (RH)，并可能导致认知障碍。尽管 RH 对海马功能有显着影响，但其潜在机制目前尚不清楚。我们的目标是确定 RH 暴露对链脲佐菌素治疗的糖尿病大鼠海马代谢的影响。方法 通过植入胰岛素丸来纠正高血糖。胰岛素治疗的糖尿病 (ITD) 大鼠每天一次暴露于轻度/中度 RH，连续 5 天。结果 RH 对海马代谢的影响显示，与对照组相比，RH 组中有 65 种代谢物发生了显着改变。与对照组相比，暴露于 RH 的 ITD 大鼠中发现属于主要途径（例如，克雷布斯循环、糖异生和氨基酸代谢）的代谢物水平存在一些显着差异。关键的糖酵解酶，包括己糖激酶、磷酸果糖激酶和丙酮酸激酶，均受到 RH 暴露的影响。结论 我们的结果表明，暴露于 RH 会导致胰岛素治疗的链脲佐菌素糖尿病大鼠海马代谢组学的改变。了解 RH 如何影响海马代谢可能有助于减轻 RH 对海马功能的不利影响。