Astrocytic 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 in glucose transport across the blood brain barrier (BBB) This was confirmed in vivo in GFAP IR KO mice by using positron emission tomography and glucose monitoring in cerebral spinal fluid. We conclude that insulin signaling in hypothalamic astrocytes co controls CNS glucose sensing and systemic glucose metabolism via regulation of glucose uptake across the BBB.
Cell