Alterations in Glucose Metabolism on Cognition: A Possible Link Between Diabetes and Dementia
Alterations in Glucose Metabolism on Cognition: A Possible Link Between Diabetes and Dementia
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DOI：
10.2174/1381612822666151209152013
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发表时间：
2016-01-01
影响因子：
3.1
通讯作者：
Barreto, George E.
中科院分区：
文献类型：
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作者：
Gonzalez-Reyes, Rodrigo E.;Aliev, Gjumrakch;Barreto, George E.
利用碳水化合物葡萄糖作为能量来源对于人体的充分功能是必不可少的。这种分子的复杂调控涉及胰腺、肝脏和大脑等各种器官的协调作用。这种生理平衡的任何破坏都可能导致一般代谢活动的危险妥协，增加发展为T1 DM、T2 DM以及可能的AD的可能性。星形胶质细胞将葡萄糖转化为乳酸，并将其转移到神经元。这种乳酸对神经元新陈代谢和各种过程是必不可少的，包括突触、树突的形成和涉及记忆的基因的表达。大脑对血糖水平的变化非常敏感，低血糖和高血糖都可能是危险的。病理性高血糖可导致血浆渗透压、线粒体产生自由基、氧化应激和激活神经细胞凋亡等改变。阿尔茨海默病和糖尿病都是以年龄为重要危险因素的慢性疾病。随着大脑年龄的增长，它似乎更容易受到循环葡萄糖过量引起的细胞损伤，这可以解释一些糖尿病患者出现认知变化的原因。在胰岛素抵抗中观察到促炎介质的过度循环，其中一些介质可能会越过血脑屏障，导致异常的神经炎症。GSK-3在糖尿病中过度表达，也被报道调节大脑中tau的磷酸化和Aβ多肽的产生。目前，糖尿病(高血糖)被认为是AD发生的危险因素。一种新的治疗方法，使用鼻腔胰岛素和抗糖尿病药物治疗阿尔茨海默病患者正在探索，并在这篇综述中讨论。
The use of the carbohydrate glucose as an energetic source is essential for an adequate function of the human body. The complex regulation of this molecule involves the coordinated action of various organs such as pancreas, liver and brain. Any disruption of this physiological balance may result in a dangerous compromise of general metabolic activities increasing the possibility of developing T1DM, T2DM and possibly AD. Astrocytes convert glucose into lactate and transfer it to neurons. This lactate is essential for neuronal metabolism and for various processes including the formation of synapses, dendrites and the expression of genes involved in memory. The brain is highly susceptible to variations in glucose blood levels, and both hypoglycemia and hyperglycemia can be dangerous. Pathological hyperglycemia induces changes in plasmatic osmotic pressure, mitochondrial production of free radicals, oxidative stress and activation of neuronal apoptosis, among others. Both AD and diabetes are chronic diseases having age as an important risk factor. As the brain ages, it seems to become much more susceptible to cellular damage induced by excess of circulating glucose and this could explain the appearance of cognitive changes observed in some patients with diabetes. Excessive circulation of pro-inflammatory agents has been observed in insulin resistance and is likely that some of these mediators may cross the blood-brain barrier and induce abnormal neuroinflammation. GSK-3 is overexpressed in diabetes and also has been reported to regulate tau phosphorylation and production of A beta peptides in the brain. Currently, diabetes (hyperglycemia) is considered as a risk factor for the development of AD. A novel therapeutic approach, using intranasal insulin and anti-diabetic medications in patients suffering from AD is being explored and is discussed in this review.