Human primary astrocytes increase basal fatty acid oxidation following recurrent low glucose to maintain intracellular nucleotide levels
Human primary astrocytes increase basal fatty acid oxidation following recurrent low glucose to maintain intracellular nucleotide levels
复制标题
人原代星形胶质细胞在反复低血糖后增加基础脂肪酸氧化以维持细胞内核苷酸水平
DOI：
10.1101/271981
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Weightman Potter P
中科院分区：
文献类型：
--
作者：
Weightman Potter P
低血糖是1型糖尿病患者良好血糖控制的主要障碍，频繁暴露于低血糖会损害对后续低血糖发作的意识。发生神经变化，以减少一个人的低血糖意识是不明确的。此外，神经胶质细胞参与低血糖感知和葡萄糖反调节的分子机制需要进一步研究。为了测试神经胶质细胞，特别是星形胶质细胞，是否可以检测到葡萄糖的变化，我们利用人原代星形胶质细胞（HPA）和U373星形细胞瘤细胞，并将它们暴露于体外复发性低葡萄糖（RLG）。这允许测量，具有高特异性和灵敏度，在细胞代谢的变化后RLG。我们报告说，AMP激活的蛋白激酶（AMPK）被激活的病理生理相关的葡萄糖浓度范围。我们观察到基础线粒体代谢对脂肪酸氧化的依赖性增加，线粒体应激的标志包括质子泄漏增加和偶联效率降低。相对于葡萄糖的利用率，乳酸释放增加，在低葡萄糖，但这是没有修改RLG，也没有葡萄糖摄取或糖原水平。总之，这些数据表明，星形胶质细胞线粒体功能障碍反复低血糖暴露后，这可能会影响低血糖葡萄糖反调节和/或低血糖意识。
Hypoglycemia is a major barrier to good glucose control in type 1 diabetes and frequent exposure to hypoglycemia can impair awareness to subsequent bouts of hypoglycemia. The neural changes that occur to reduce a person’s awareness of hypoglycemia are poorly defined. Moreover, the molecular mechanisms by which glial cells contribute to hypoglycemia sensing and glucose counterregulation require further investigation. To test whether glia, specifically astrocytes, could detect changes in glucose, we utilized human primary astrocytes (HPA) and U373 astrocytoma cells and exposed them to recurrent low glucose (RLG)in vitro. This allowed measurement, with high specificity and sensitivity, of changes in cellular metabolism following RLG. We report that the AMP-activated protein kinase (AMPK) is activated over a pathophysiologically-relevant glucose concentration range. We observed an increased dependency on fatty acid oxidation for basal mitochondrial metabolism and hallmarks of mitochondrial stress including increased proton leak and reduced coupling efficiency. Relative to glucose availability, lactate release increased during low glucose but this was not modified by RLG, nor were glucose uptake or glycogen levels. Taken together, these data indicate that astrocyte mitochondria are dysfunctional following recurrent low glucose exposure, which could have implications for hypoglycemia glucose counterregulation and/or hypoglycemia awareness.
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影响因子：
15.9
作者：
Claret, Marc;Smith, Mark A.;Withers, Dominic J.
通讯作者：
Withers, Dominic J.
下丘脑神经胶质细胞中的葡萄糖转运蛋白1介导葡萄糖传感，以调节体内葡萄糖的产生。
影响因子：
7.7
作者：
Chari M;Yang CS;Lam CK;Lee K;Mighiu P;Kokorovic A;Cheung GW;Lai TY;Wang PY;Lam TK
通讯作者：
Lam TK
纳洛酮（而非缬沙坦）在既往低血糖后保留对低血糖的反应
影响因子：
7.7
作者：
M. Poplawski;J. Mastaitis;C. Mobbs
通讯作者：
C. Mobbs
影响因子：
4.2
作者：
Canada, Sarah E.;Weaver, Staci A.;Sharpe, Shannon N.;Pederson, Bartholomew A.
通讯作者：
Pederson, Bartholomew A.
影响因子：
8.2
作者：
Robinson, RTCE;Harris, ND;Heller, SR
通讯作者：
Heller, SR