Department of Endocrinology, Fujian Medical University Union Hospital, Fuzhou, China.
Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fujian Medical University, Fuzhou, China.
Biochem Biophys Res Commun. 2023 Nov 19;682:325-334. doi: 10.1016/j.bbrc.2023.10.036. Epub 2023 Oct 10.
Hypoglycemia is a common adverse reaction to glucose-lowering treatment. Diabetes mellitus (DM) combined with recurrent nonsevere hypoglycemia (RH) can accelerate cognitive decline. Currently, the metabolic pattern changes in cognition-related brain regions caused by this combined effect of DM and RH (DR) remain unclear. In this study, we first characterized the metabolic profiles of the hippocampus in mice exposed to DR using non-targeted metabolomic platforms. Our results showed that DR induced a unique metabolic pattern in the hippocampus, and several significant differences in metabolite levels belonging to the histidine metabolism pathway were discovered. Based on these findings, in the follow-up experiment, we found that histidine treatment could attenuate the cognitive impairment and rescue the neuronal and synaptic damage induced by DR in the hippocampus, which are closely related to ameliorated mitochondrial injury. These findings provide new insights into the metabolic mechanisms of the hippocampus in the progression of DR, and l-histidine supplementation may be a potential metabolic therapy in the future.
低血糖是降糖治疗的常见不良反应。糖尿病（DM）合并反复无严重低血糖（RH）可加速认知功能下降。目前，DM 和 RH 联合作用（DR）引起的与认知相关的脑区代谢模式变化尚不清楚。在这项研究中，我们首先使用非靶向代谢组学平台对暴露于 DR 的小鼠海马中的代谢谱进行了特征描述。我们的结果表明，DR 在海马中诱导了一种独特的代谢模式，并发现了几种属于组氨酸代谢途径的代谢物水平的显著差异。基于这些发现，在后续实验中，我们发现组氨酸治疗可以减轻 DR 引起的认知障碍，并挽救海马中的神经元和突触损伤，这与改善线粒体损伤密切相关。这些发现为 DR 进展中海马的代谢机制提供了新的见解，补充 l-组氨酸可能是未来一种有潜力的代谢治疗方法。
