ArticleScientific reports2019
Hypoglycemia-activated Hypothalamic Microglia Impairs Glucose Counterregulatory Responses.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- A Hypothalamic Inhibitory Circuit Encoding the Scalability of Stress Responses.bioRxiv : the preprint server for biology · 2026Article
- THIK-1 channel mediates microglial glucose sensing and modulates AgRP neurons.bioRxiv : the preprint server for biology · 2026Article
- Examining a central mechanism whereby undernutrition inhibits GnRH secretion via KNDy neurons.The Journal of reproduction and development · 2026Review
- Hypothalamic Prostaglandins Facilitate Recovery From Severe Hypoglycemia but Exacerbate Recurrent Hypoglycemia in Mice.Diabetes · 2025Article
- Review
- Neuropathological changes in the nucleus basalis of Meynert in people with type 1 or type 2 diabetes mellitus.Acta neuropathologica · 2025Article
- Microglial Modulation as a Therapeutic Avenue for Perioperative Neurocognitive Disorders: Unveiling Pathophysiological Mechanisms and Clinical Implications.CNS neuroscience & therapeutics · 2025Review
- Executive Function Response to Moderate-to-High-Intensity Rope Skipping in Overweight Adolescents Aged 12-14: A Preliminary Study.Journal of functional morphology and kinesiology · 2025Article
- Persistently increased post-stress activity of paraventricular thalamic neurons is essential for the emergence of stress-induced alterations in behaviour.PLoS biology · 2025Article
- Acute severe hypoglycemia alters mouse brain microvascular proteome.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Microglia in physiological conditions and the importance of understanding their homeostatic functions in the arcuate nucleus.Frontiers in immunology · 2024Review
- Microglia in Central Control of Metabolism.Physiology (Bethesda, Md.) · 2024Review
- Obesity-associated microglial inflammatory activation paradoxically improves glucose tolerance.Cell metabolism · 2023Article
- TREM2 deficiency inhibits microglial activation and aggravates demyelinating injury in neuromyelitis optica spectrum disorder.Journal of neuroinflammation · 2023Article
- Review
- Lipid biosynthesis enzyme Agpat5 in AgRP-neurons is required for insulin-induced hypoglycemia sensing and glucagon secretion.Nature communications · 2022Article
- Hypothalamic Irak4 is a genetically controlled regulator of hypoglycemia-induced glucagon secretion.Molecular metabolism · 2022Article
- Recent advances in understanding hypothalamic control of defensive responses to hypoglycaemia.Current opinion in endocrine and metabolic research · 2022Review
- Homeostatic Regulation of Glucose Metabolism by the Central Nervous System.Endocrinology and metabolism (Seoul, Korea) · 2022Article
- Regulation of the Fructose Transporter GeneInternational journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucose is a major fuel for the central nervous system and hypoglycemia is a significant homeostatic stressor, which elicits counterregulatory reactions. Hypothalamic metabolic- and stress-related neurons initiate these actions, however recruitment of glia in control such adaptive circuit remain unknown. Groups of fed- and fasted-, vehicle-injected, and fasted + insulin-injected male mice were compared in this study. Bolus insulin administration to fasted mice resulted in hypoglycemia, which increased hypothalamo-pituitary-adrenal (HPA) axis- and sympathetic activity, increased transcription of neuropeptide Y (Npy) and agouti-related peptide (Agrp) in the hypothalamic arcuate nucleus and activated IBA1+ microglia in the hypothalamus. Activated microglia were found in close apposition to hypoglycemia-responsive NPY neurons. Inhibition of microglia by minocycline increased counterregulatory sympathetic response to hypoglycemia. Fractalkine-CX3CR1 signaling plays a role in control of microglia during hypoglycemia, because density and solidity of IBA1-ir profiles was attenuated in fasted, insulin-treated, CX3CR1 KO mice, which was parallel with exaggerated neuropeptide responses and higher blood glucose levels following insulin administration. Hypoglycemia increased Il-1b expression in the arcuate nucleus, while IL-1a/b knockout mice display improved glycemic control to insulin administration. In conclusion, activated microglia in the arcuate nucleus interferes with central counterregulatory responses to hypoglycemia. These results underscore involvement of microglia in hypothalamic regulation of glucose homeostasis.
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