ArticleEndocrinology2018
Estradiol Protects Proopiomelanocortin Neurons Against Insulin Resistance.
Article in Endocrinology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 60 citations in OpenAlex.
- 17α-Estradiol: A mildly feminizing estrogen with sex-specific metabolic and lifespan benefits.Ageing research reviews · 2026Review
- Neuroendocrine crosstalk between sex and metabolic hormones: mechanisms and implications across the female reproductive spectrum.Discover endocrinology and metabolism · 2026Review
- Multidimensional Effects of Stress on Neuronal Exosome Levels and Simultaneous Transcriptomic Profiles.Biological psychiatry global open science · 2025Article
- Canonical transient receptor potential channels and hypothalamic control of homeostatic functions.Journal of neuroendocrinology · 2024Review
- Insulin-Heart Axis: Bridging Physiology to Insulin Resistance.International journal of molecular sciences · 2024Review
- ZFYVE28 mediates insulin resistance by promoting phosphorylated insulin receptor degradation via increasing late endosomes production.Nature communications · 2023Article
- Role of Estrogen Receptor α in Aging and Chronic Disease.Advances in geriatric medicine and research · 2023Article
- Neuroendocrine microRNAs linked to energy homeostasis: future therapeutic potential.Pharmacological reports : PR · 2022Review
- Sexual Dimorphism in Adipose-Hypothalamic Crosstalk and the Contribution of Aryl Hydrocarbon Receptor to Regulate Energy Homeostasis.International journal of molecular sciences · 2022Review
- Trends in insulin resistance: insights into mechanisms and therapeutic strategy.Signal transduction and targeted therapy · 2022Review
- The hypothalamus for whole-body physiology: from metabolism to aging.Protein & cell · 2022Review
- Estrogenic regulation of reproduction and energy homeostasis by a triumvirate of hypothalamic arcuate neurons.Journal of neuroendocrinology · 2022Review
- Insulin action in the brain: cell types, circuits, and diseases.Trends in neurosciences · 2022Review
- Loss of Microglial Insulin Receptor Leads to Sex-Dependent Metabolic Disorders in Obese Mice.International journal of molecular sciences · 2022Article
- The PACAP Paradox: Dynamic and Surprisingly Pleiotropic Actions in the Central Regulation of Energy Homeostasis.Frontiers in endocrinology · 2022Review
- Pituitary Adenylate Cyclase Activating Polypeptide Inhibits ANeuroscience · 2021Article
- Deletion ofThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- The influence of estrogen receptor α signaling independent of the estrogen response element on avoidance behavior, social interactions, and palatable ingestive behavior in female mice.Hormones and behavior · 2021Article
- CRISPR knockdown of Kcnq3 attenuates the M-current and increases excitability of NPY/AgRP neurons to alter energy balance.Molecular metabolism · 2021Article
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8 authors at 3 institutions in 1 country.
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Abstract
Insulin resistance is at the core of the metabolic syndrome, and men exhibit a higher incidence of metabolic syndrome than women in early adult life, but this sex advantage diminishes sharply when women reach the postmenopausal state. Because 17β-estradiol (E2) augments the excitability of the anorexigenic proopiomelanocortin (POMC) neurons, we investigated the neuroprotective effects of E2 against insulin resistance in POMC neurons from diet-induced obese (DIO) female and male mice. The efficacy of insulin to activate canonical transient receptor potential 5 (TRPC5) channels and depolarize POMC neurons was significantly reduced in DIO male mice but not in DIO female mice. However, the insulin response in POMC neurons was abrogated in ovariectomized DIO females but restored with E2 replacement. E2 increased T-type calcium channel Cav3.1 messenger RNA (mRNA) expression and whole-cell currents but downregulated stromal-interaction molecule 1 mRNA, which rendered POMC neurons more excitable and responsive to insulin-mediated TRPC5 channel activation. Moreover, E2 prevented the increase in suppressor of cytokine signaling-3 mRNA expression with DIO as seen in DIO males. As proof of principle, insulin [intracerebroventricular injection into the third ventricle (ICV)] decreased food intake and increased metabolism in female but not male guinea pigs fed a high-fat diet. The uncoupling of the insulin receptor from its downstream effector system was corroborated by the reduced expression of phosphorylated protein kinase B in the arcuate nucleus of male but not female guinea pigs following insulin. Therefore, E2 protects female POMC neurons from insulin resistance by enhancing POMC neuronal excitability and the coupling of insulin receptor to TRPC5 channel activation.
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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.