ArticlePLoS biology2019
Ablating astrocyte insulin receptors leads to delayed puberty and hypogonadism in mice.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 48 citations in OpenAlex.
- Hypothalamic control of puberty: from neuronal circuits to mechanisms for its metabolic regulation.Reviews in endocrine & metabolic disorders · 2026Review
- Hypothalamic neuroimmune remodeling as an immunometabolic bridge between childhood obesity and earlier pubertal onset.Frontiers in immunology · 2026Review
- Association Between Metabolic Score for Insulin Resistance (METS-IR) and Risk of Infertility: Evidence from NHANES 2013-2020 and Mendelian Randomization Study.International journal of women's health · 2026Article
- Changes in social reward across adolescence in male mice.Scientific reports · 2025Article
- The dual burden of obesity: decoding metabolism and female reproductive endocrinology.Frontiers in physiology · 2025Review
- Kisspeptin signaling in astrocytes modulates the reproductive axis.The Journal of clinical investigation · 2024Article
- Metabolic control of puberty: 60 years in the footsteps of Kennedy and Mitra's seminal work.Nature reviews. Endocrinology · 2024Review
- Metabolic hormones are integral regulators of female reproductive health and function.Bioscience reports · 2024Review
- A cardiac amino-terminal GRK2 peptide inhibits insulin resistance yet enhances maladaptive cardiovascular and brown adipose tissue remodeling in females during diet-induced obesity.Journal of molecular and cellular cardiology · 2023Review
- The Expression of Insulin in the Central Nervous System: What Have We Learned So Far?International journal of molecular sciences · 2023Review
- The Significance of Hypothalamic Inflammation and Gliosis for the Pathogenesis of Obesity in Humans.Endocrine reviews · 2023Review
- The contribution of astrocytes to obesity-associated metabolic disturbances.Journal of biomedical research · 2022Article
- Insulin regulates neurovascular coupling through astrocytes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Insulin action in the brain: cell types, circuits, and diseases.Trends in neurosciences · 2022Review
- Peripheral Insulin Regulates a Broad Network of Gene Expression in Hypothalamus, Hippocampus, and Nucleus Accumbens.Diabetes · 2021Article
- Pituitary P62 deficiency leads to female infertility by impairing luteinizing hormone production.Experimental & molecular medicine · 2021Article
- Insulin action in the brain regulates both central and peripheral functions.American journal of physiology. Endocrinology and metabolism · 2021Review
- Insulin sensing by astrocytes is critical for normal thermogenesis and body temperature regulation.The Journal of endocrinology · 2020Article
- The Genetic Basis of Delayed Puberty.Frontiers in endocrinology · 2019Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Insulin resistance and obesity are associated with reduced gonadotropin-releasing hormone (GnRH) release and infertility. Mice that lack insulin receptors (IRs) throughout development in both neuronal and non-neuronal brain cells are known to exhibit subfertility due to hypogonadotropic hypogonadism. However, attempts to recapitulate this phenotype by targeting specific neurons have failed. To determine whether astrocytic insulin sensing plays a role in the regulation of fertility, we generated mice lacking IRs in astrocytes (astrocyte-specific insulin receptor deletion [IRKOGFAP] mice). IRKOGFAP males and females showed a delay in balanopreputial separation or vaginal opening and first estrous, respectively. In adulthood, IRKOGFAP female mice also exhibited longer, irregular estrus cycles, decreased pregnancy rates, and reduced litter sizes. IRKOGFAP mice show normal sexual behavior but hypothalamic-pituitary-gonadotropin (HPG) axis dysregulation, likely explaining their low fecundity. Histological examination of testes and ovaries showed impaired spermatogenesis and ovarian follicle maturation. Finally, reduced prostaglandin E synthase 2 (PGES2) levels were found in astrocytes isolated from these mice, suggesting a mechanism for low GnRH/luteinizing hormone (LH) secretion. These findings demonstrate that insulin sensing by astrocytes is indispensable for the function of the reproductive axis. Additional work is needed to elucidate the role of astrocytes in the maturation of hypothalamic reproductive circuits.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.