Role of ketone bodies in diabetes-induced dementia: sirtuins, insulin resistance, synaptic plasticity, mitochondrial dysfunction, and neurotransmitter.
Role of ketone bodies in diabetes-induced dementia: sirtuins, insulin resistance, synaptic plasticity, mitochondrial dysfunction, and neurotransmitter.
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DOI：
10.1093/nutrit/nuab118
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发表时间：
2022-03-10
影响因子：
6.1
通讯作者：
Song J
中科院分区：
文献类型：
--
作者：
Chung JY;Kim OY;Song J
2型糖尿病患者可能有几种神经病变，如记忆缺陷。最近的研究集中在代谢失衡和神经病理学问题之间的关联，以及相关的分子病理学。糖尿病引发神经炎症、突触可塑性受损、线粒体功能障碍和脑中的胰岛素抵抗。葡萄糖是神经元的主要能量底物，但在某些条件下，如禁食和饥饿，酮体可用作这些细胞的能量燃料。最近的证据揭示了酮体在调节几种抗炎细胞通路和改善葡萄糖代谢、胰岛素作用和突触可塑性中的作用，从而具有神经保护作用。然而，非常大量的酮体可能对大脑有毒，例如酮症酸中毒，这是一种可能发生在1型糖尿病或酒精中毒中的危险并发症。本文综述了近年来有关酮体与痴呆神经发病机制关系的研究进展。他们认为，考虑到酮体在中枢神经系统中的多方面影响，足够低量的酮体可以成为治疗糖尿病诱导的痴呆神经病理学的潜在能量来源。本综述可为糖尿病性痴呆生酮饮食治疗指南的制定提供参考。
Patients with type 2 diabetes can have several neuropathologies, such as memory deficits. Recent studies have focused on the association between metabolic imbalance and neuropathological problems, and the associated molecular pathology. Diabetes triggers neuroinflammation, impaired synaptic plasticity, mitochondrial dysfunction, and insulin resistance in the brain. Glucose is a main energy substrate for neurons, but under certain conditions, such as fasting and starvation, ketone bodies can be used as an energy fuel for these cells. Recent evidence has shed new light on the role of ketone bodies in regulating several anti-inflammation cellular pathways and improving glucose metabolism, insulin action, and synaptic plasticity, thereby being neuroprotective. However, very high amount of ketone bodies can be toxic for the brain, such as in ketoacidosis, a dangerous complication that may occur in type 1 diabetes mellitus or alcoholism. Recent findings regarding the relationship between ketone bodies and neuropathogenesis in dementia are reviewed in this article. They suggest that the adequately low amount of ketone bodies can be a potential energy source for the treatment of diabetes-induced dementia neuropathology, considering the multifaceted effects of the ketone bodies in the central nervous system. This review can provide useful information for establishing the therapeutic guidelines of a ketogenic diet for diabetes-induced dementia.
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