ArticleMolecular brain2016
Wnt3a upregulates brain-derived insulin by increasing NeuroD1 via Wnt/β-catenin signaling in the hypothalamus.
Article in Molecular brain, 2016. 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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19 citing papers in PubMed, 31 citations in OpenAlex.
- Assessment of the Association of Periodontitis and Diabetes Mellitus with Alzheimer's Disease in a Mouse Model.International journal of molecular sciences · 2026Article
- Electroacupuncture ameliorates cognitive dysfunction in T2DM rats by modulating astrocytic polarization and aberrant energy metabolism in the hippocampus via the Wnt/β-catenin pathway.Diabetology & metabolic syndrome · 2025Article
- Ultrasound-Responsive Polymeric Piezoelectric Nanoparticles for Remote Activation and Neuronal Differentiation of Human Neural Stem Cells.Small science · 2025Article
- Exendin-4 ameliorates tau hyperphosphorylation and cognitive impairment in type 2 diabetes through acting on Wnt/β-catenin/NeuroD1 pathway.Molecular medicine (Cambridge, Mass.) · 2023Article
- The Expression of Insulin in the Central Nervous System: What Have We Learned So Far?International journal of molecular sciences · 2023Review
- From attention-deficit hyperactivity disorder to sporadic Alzheimer's disease-Wnt/mTOR pathways hypothesis.Frontiers in neuroscience · 2023Article
- The bHLH Transcription Factors in Neural Development and Therapeutic Applications for Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- The Flavonol Quercitrin Hinders GSK3 Activity and Potentiates the Wnt/β-Catenin Signaling Pathway.International journal of molecular sciences · 2022Article
- Silencing of hypothalamic FGF11 prevents diet-induced obesity.Molecular brain · 2022Article
- Insulin synthesized in the paraventricular nucleus of the hypothalamus regulates pituitary growth hormone production.JCI insight · 2020Article
- Changes in nucleus accumbens gene expression accompany sex-specific suppression of spontaneous physical activity in aromatase knockout mice.Hormones and behavior · 2020Article
- Novel Mouse miRNA Chr13_novelMiR7354-5p Improves Bone-Marrow-Derived Mesenchymal Stem Cell Differentiation into Insulin-Producing Cells.Molecular therapy. Nucleic acids · 2020Article
- GSK3β Inhibition Restores Impaired Neurogenesis in Preterm Neonates With Intraventricular Hemorrhage.Cerebral cortex (New York, N.Y. : 1991) · 2019Article
- Palmitate-induced autophagy liberates monounsaturated fatty acids and increasesAnimal cells and systems · 2019Article
- Glycogen synthase kinase-3β inhibition enhances myelination in preterm newborns with intraventricular hemorrhage, but not recombinant Wnt3A.Neurobiology of disease · 2018Article
- Effect of developmental NMDAR antagonism with CGP 39551 on aspartame-induced hypothalamic and adrenal gene expression.PloS one · 2018Article
- Hypothalamic AMPK-induced autophagy increases food intake by regulating NPY and POMC expression.Autophagy · 2016Article
- Type 2 Diabetes, Cognition, and Dementia in Older Adults: Toward a Precision Health Approach.Diabetes spectrum : a publication of the American Diabetes Association · 2016Article
- Commentary: The Flavonoid Baicalein Rescues Synaptic Plasticity and Memory Deficits in a Mouse Model of Alzheimer's Disease.Frontiers in neurology · 2016Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInsulin plays diverse roles in the brain. Although insulin produced by pancreatic β-cells that crosses the blood-brain barrier is a major source of brain insulin, recent studies suggest that insulin is also produced locally within the brain. However, the mechanisms underlying the production of brain-derived insulin (BDI) are not yet known.
resultsHere, we examined the effect of Wnt3a on BDI production in a hypothalamic cell line and hypothalamic tissue. In N39 hypothalamic cells, Wnt3a treatment significantly increased the expression of the Ins2 gene, which encodes the insulin isoform predominant in the mouse brain, by activating Wnt/β-catenin signaling. The concentration of insulin was higher in culture medium of Wnt3a-treated cells than in that of untreated cells. Interestingly, neurogenic differentiation 1 (NeuroD1), a target of Wnt/β-catenin signaling and one of transcription factors for insulin, was also induced by Wnt3a treatment in a time- and dose-dependent manner. In addition, the treatment of BIO, a GSK3 inhibitor, also increased the expression of Ins2 and NeuroD1. Knockdown of NeuroD1 by lentiviral shRNAs reduced the basal expression of Ins2 and suppressed Wnt3a-induced Ins2 expression. To confirm the Wnt3a-induced increase in Ins2 expression in vivo, Wnt3a was injected into the hypothalamus of mice. Wnt3a increased the expression of NeuroD1 and Ins2 in the hypothalamus in a manner similar to that observed in vitro.
conclusionTaken together, these results suggest that BDI production is regulated by the Wnt/β-catenin/NeuroD1 pathway in the hypothalamus. Our findings will help to unravel the regulation of BDI production in the hypothalamus.
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