Glucose Transporter-2 Regulation of Male versus Female Hypothalamic Astrocyte MAPK Expression and Activation: Impact of Glucose

The plasma membrane glucose transporter (GLUT)-2 is unique among GLUT family proteins in that it also functions as a sensor. GLUT2 imposes sex-dimorphic control of hypothalamic astrocyte storage and catabolism by unknown mechanisms. Mitogen-activated protein kinase (MAPK) signaling cascades operate within stress-sensitive signal transduction pathways. present study employed an established primary culture model gene knockdown tools to investigate whether one or more the three MAP families are regulated GLUT2. caused opposing adjustments total ERK1/2 glucose-supplied male versus female astrocytes, augmenting reducing mean phosphorylated/total ratio for 44 42 kDa variants these sexes. Glucose deprivation amplified this both variants, albeit larger magnitude males; siRNA exacerbated stimulatory response males only. Phosphorylated/total p38 MAPK ratios were up-regulated male, but not astrocytes. Glucose-deprived astrocytes exhibited no change (male) reduction (female) after silencing. increased 54 46 SAPK/JNK each sex when was present. However, withdrawal suppressed ratios, while attenuated inverse responses. results show inhibits ERK1/2, p38, activity differentially stimulates pathways Glucoprivation induces divergent activities. findings demonstrate role activation glucose-starved can act either inhibitor inducer glucose-deprived glial cells, respectively.