1] CNRS, UMR6265, CSGA, Dijon, France [2] INRA, UMR1324, CSGA, Dijon, France [3] Université de Bourgogne, CSGA, Dijon, France.
1] Collège de France, Center for Interdisciplinary Research in Biology (CIRB)/Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241/Institut National de la Santé et de la Recherche Médicale U1050, 75231 Paris Cedex 05, Paris, France [2] University Pierre et Marie Curie, ED, N 158, Paris, France [3] MEMOLIFE Laboratory of Excellence and Paris Science Lettre Research University, Paris, France.
J Cereb Blood Flow Metab. 2014 Feb;34(2):339-46. doi: 10.1038/jcbfm.2013.206. Epub 2013 Dec 4.
Hypothalamic glucose detection participates in maintaining glycemic balance, food intake, and thermogenesis. Although hypothalamic neurons are the executive cells involved in these responses, there is increasing evidence that astrocytes participate in glucose sensing (GS); however, it is unknown whether astroglial networking is required for glucose sensitivity. Astroglial connexins 30 and 43 (Cx30 and Cx43) form hexameric channels, which are apposed in gap junctions, allowing for the intercellular transfer of small molecules such as glucose throughout the astroglial networks. Here, we hypothesized that hypothalamic glucose sensitivity requires these connexins. First, we showed that both Cxs are enriched in the rat hypothalamus, with highly concentrated Cx43 expression around blood vessels of the mediobasal hypothalamus (MBH). Both fasting and high glycemic levels rapidly altered the protein levels of MBH astroglial connexins, suggesting cross talk within the MBH between glycemic status and the connexins' ability to dispatch glucose. Finally, the inhibition of MBH Cx43 (by transient RNA interference) attenuated hypothalamic glucose sensitivity in rats, which was demonstrated by a pronounced decreased insulin secretion in response to a brain glucose challenge. These results illustrate that astroglial connexins contribute to hypothalamic GS.
下丘脑葡萄糖检测参与维持血糖平衡、摄食和产热。尽管下丘脑神经元是参与这些反应的执行细胞，但越来越多的证据表明星形胶质细胞参与葡萄糖感应（GS）；然而，尚不清楚星形胶质细胞网络是否是葡萄糖敏感性所必需的。星形胶质细胞连接蛋白 30 和 43（Cx30 和 Cx43）形成六聚体通道，这些通道在缝隙连接中相对，允许小分子（如葡萄糖）在整个星形胶质细胞网络中进行细胞间转移。在这里，我们假设下丘脑的葡萄糖敏感性需要这些连接蛋白。首先，我们表明 Cx 均在大鼠下丘脑中富集，Cx43 在中脑基底部下丘脑（MBH）血管周围的表达高度集中。禁食和高血糖水平都会迅速改变 MBH 星形胶质细胞连接蛋白的蛋白水平，这表明血糖状态与连接蛋白传递葡萄糖的能力之间在 MBH 内存在交叉对话。最后，通过短暂的 RNA 干扰抑制 MBH Cx43 减弱了大鼠的下丘脑葡萄糖敏感性，这表现为对脑葡萄糖挑战的胰岛素分泌明显减少。这些结果表明星形胶质细胞连接蛋白有助于下丘脑 GS。
