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. 2016 Sep 28;6:34138. doi: 10.1038/srep34138

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Copyright © 2016, The Author(s)

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(A) The glucose-sensing pathway in the capillary-astrocytes-neurons axis. Blood glucose in the vessels reaches the hypothalamus through endothelial Slc2a1 (also known as Glut1). Slc2a1, also expressed in astrocytic endfeet around the blood vessels, can detect and transport glucose into the astrocytes. After transport into the cells, the glucose is quickly phosphorylated by the hexokinase (Hk1/2) or glucokinase (Gck) in the astrocytes. The phosphorylation of glucose then results in enrichment of Gja1 (known as Cx43) in the astroglial endfeet wrapping the blood vessels. Lactate, which is metabolized by glucose in a series of enzymatic steps, can cross into the astrocytes by both Gja1 and Gjb6 (Cx30) gap-junctions or alternatively can be transported to the extracellular space with the help of astroglial Slc161/3 (Mct1/3). Finally, the extracellular lactate was transported through Slc16a7(Mct2) into the glucose-sensitive neurons (GSN). The oxidation of lactate further regulates the GSN electrical activity. Additionally, Slc2a3 (Glut3), which was expressed in the GSN, can detect and transport glucose released from the astrocytes through Gja1 or the freely diffusing glucose at the endothelial site. Upon neuronal activation, the glutamate release from the GSN will be detected and transported into the astrocytes by astroglial Slc1a2 or Slc1a3, and it will further influence the expression of Gja1 in the astrocytes. (B) The gene expression in the hypothalamic glucose-sensing pathway. (C) The fold change and the corresponding p-value of each gene in GK rats compared with Wistar rats.