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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961449PMC
http://dx.doi.org/10.1016/j.cell.2016.07.028DOI Listing

Publication Analysis

Top Keywords

insulin signaling
12
glucose
10
astrocytic insulin
8
glucose uptake
8
glucose sensing
8
sensing systemic
8
systemic glucose
8
glucose metabolism
8
postnatal ablation
8
astrocytic irs
8

Similar Publications

Pumpkin extract has been shown to alleviate hyperglycemic symptoms by improving glucose metabolism disorders. However, the specific active components responsible for its hypoglycemic effects and the underlying molecular mechanisms remain unclear. In this study, db/db mice underwent a 4-week dietary intervention with two pumpkin flours (PF1 and PF2), total dietary fiber (TDF), soluble dietary fiber (SDF), and insoluble dietary fiber (IDF), with acarbose serving as a positive control.

View Article and Find Full Text PDF

The influence of interleukin-27 on metabolic fitness in a murine neonatal model of bacterial sepsis.

Am J Physiol Endocrinol Metab

January 2025

Department of Microbiology, Immunology, & Cell Biology, West Virginia University School of Medicine, 64 Medical Center Drive, Morgantown, WV, 26506, USA.

Human neonates are predisposed to an increased risk of mortality from infection due to fundamental differences in the framework of innate and adaptive immune responses relative to those in the adult population. As one key difference in neonates, an increase in the immunosuppressive cytokine, IL-27, is responsible for poor outcomes in a murine neonatal model of bacterial sepsis. In our model, the absence of IL-27 signaling during infection is associated with improved maintenance of body mass, increased bacterial clearance with reduced systemic inflammation, and decreased mortality rates that correlate to preservation of glucose homeostasis and insulin production.

View Article and Find Full Text PDF

Association between Mediterranean diet and metabolic health status among adults was not mediated through serum adropin levels.

BMC Public Health

January 2025

Department of Community Nutrition, School of Nutrition and Food Science, Nutrition and Food Security Research Center, Isfahan University of Medical Sciences, PO Box 81745-151, Isfahan, Iran.

Background: Prevalence of metabolic disorders has been increased in recent years around the world. The relationship between Mediterranean diet (MD) with metabolic health status and serum adropin levels has been less examined in Iranian adults. We investigated the association between MD compliance with metabolic health status and adropin hormone in Iranian adults.

View Article and Find Full Text PDF

Investigating the genetic factors influencing human birth weight may lead to biological insights into fetal growth and long-term health. We report analyses of rare variants that impact birth weight when carried by either fetus or mother, using whole exome sequencing data in up to 234,675 participants. Rare protein-truncating and deleterious missense variants are collapsed to perform gene burden tests.

View Article and Find Full Text PDF

Anxiety disorder, a prevalent mental health issue, is one of the leading causes of disability worldwide. Damage to the blood-brain barrier (BBB) is implicated in anxiety, but its regulatory mechanisms remain unclear. Herein, we show that adrenomedullin 2 (ADM2), a novel angiogenic growth factor, alleviates autistic and anxiety-like behaviors in mice.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!