biostudies-literatureGarcia-Caceres CNIDDK NIH HHS867-880https://www.ebi.ac.uk/biostudies/studies/S-EPMC8961449biostudies-literatureUnknown166(4)We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in glial fibrillary acidic protein (GFAP)-expressing cells affects hypothalamic astrocyte morphology, mitochondrial function, and circuit connectivity. Accordingly, astrocytic IR ablation reduces glucose-induced activation of hypothalamic pro-opio-melanocortin (POMC) neurons and impairs physiological responses to changes in glucose availability. Hypothalamus-specific knockout of astrocytic IRs, as well as postnatal ablation by targeting glutamate aspartate transporter (GLAST)-expressing cells, replicates such alterations. A normal response to altering directly CNS glucose levels in mice lacking astrocytic IRs indicates a role iCellAstrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability.PMC8961449P30 DK036836R01 DK031036Gotz MLuquet SNinkovic JMeyer CWGruber TLe Thuc OFernandez AMGarcia-Caceres CJastroch MYi CXWoods SCVarela LLegutko BKahn CRSzigeti-Buck KGao YJohansson PPfluger PTTschop MHQuarta CCai WTorres-Aleman IHorvath TLfalseAstrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability.We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in glial fibrillary acidic protein (GFAP)-expressing cells affects hypothalamic astrocyte morphology, mitochondrial function, and circuit connectivity. Accordingly, astrocytic IR ablation reduces glucose-induced activation of hypothalamic pro-opio-melanocortin (POMC) neurons and impairs physiological responses to changes in glucose availability. Hypothalamus-specific knockout of astrocytic IRs, as well as postnatal ablation by targeting glutamate aspartate transporter (GLAST)-expressing cells, replicates such alterations. A normal response to altering directly CNS glucose levels in mice lacking astrocytic IRs indicates a role i2016-01-01T00:00:00Z2016 Aug2025-04-05T16:00:15.754Z2025-04-05T16:00:15.754ZS-EPMC89614492751856210.1016/j.cell.2016.07.028