Laboratorio de Biología Celular, Departamento de Biología Celular, Universidad de Concepción, Concepción, Chile.
PLoS One. 2011 Jan 28;6(1):e16411. doi: 10.1371/journal.pone.0016411.
Metabolic interaction via lactate between glial cells and neurons has been proposed as one of the mechanisms involved in hypothalamic glucosensing. We have postulated that hypothalamic glial cells, also known as tanycytes, produce lactate by glycolytic metabolism of glucose. Transfer of lactate to neighboring neurons stimulates ATP synthesis and thus contributes to their activation. Because destruction of third ventricle (III-V) tanycytes is sufficient to alter blood glucose levels and food intake in rats, it is hypothesized that tanycytes are involved in the hypothalamic glucose sensing mechanism. Here, we demonstrate the presence and function of monocarboxylate transporters (MCTs) in tanycytes. Specifically, MCT1 and MCT4 expression as well as their distribution were analyzed in Sprague Dawley rat brain, and we demonstrate that both transporters are expressed in tanycytes. Using primary tanycyte cultures, kinetic analyses and sensitivity to inhibitors were undertaken to confirm that MCT1 and MCT4 were functional for lactate influx. Additionally, physiological concentrations of glucose induced lactate efflux in cultured tanycytes, which was inhibited by classical MCT inhibitors. Because the expression of both MCT1 and MCT4 has been linked to lactate efflux, we propose that tanycytes participate in glucose sensing based on a metabolic interaction with neurons of the arcuate nucleus, which are stimulated by lactate released from MCT1 and MCT4-expressing tanycytes.
胶质细胞和神经元之间通过乳酸的代谢相互作用被认为是参与下丘脑葡萄糖感应的机制之一。我们假设下丘脑胶质细胞,也称为室管膜细胞,通过葡萄糖的糖酵解代谢产生乳酸。乳酸向邻近神经元的转移刺激 ATP 合成,从而有助于神经元的激活。由于破坏第三脑室 (III-V) 室管膜细胞足以改变大鼠的血糖水平和摄食量,因此假设室管膜细胞参与了下丘脑葡萄糖感应机制。在这里,我们证明了单羧酸转运蛋白 (MCT) 在室管膜细胞中的存在和功能。具体来说,分析了 Sprague Dawley 大鼠脑中单羧酸转运蛋白 1 (MCT1) 和单羧酸转运蛋白 4 (MCT4) 的表达及其分布,并证明这两种转运蛋白均在室管膜细胞中表达。使用原代室管膜细胞培养物进行了动力学分析和对抑制剂的敏感性分析,以确认 MCT1 和 MCT4 可用于乳酸的内流。此外,生理浓度的葡萄糖诱导培养的室管膜细胞中乳酸的外流,而经典 MCT 抑制剂可抑制这种外流。由于 MCT1 和 MCT4 的表达都与乳酸的外流有关,因此我们提出,室管膜细胞可能通过与弓状核神经元的代谢相互作用参与葡萄糖感应,而弓状核神经元则受到来自表达 MCT1 和 MCT4 的室管膜细胞释放的乳酸的刺激。
Cell Biosci. 2022-5-26
Sci Rep. 2021-11-4
J Clin Invest. 2021-9-15
Am J Physiol Endocrinol Metab. 2008-8
Int Rev Cytol. 2005
Philos Trans R Soc Lond B Biol Sci. 2005-12-29
Science. 2005-8-5