Cited 3 time in webofscience Cited 1 time in scopus

Wnt3a upregulates brain-derived insulin by increasing NeuroD1 via Wnt/beta-catenin signaling in the hypothalamus

Title
Wnt3a upregulates brain-derived insulin by increasing NeuroD1 via Wnt/beta-catenin signaling in the hypothalamus
Authors
Lee, J[Lee, Jaemeun]Kim, K[Kim, Kyungchan]Yu, SW[Yu, Seong-Woon]Kim, EK[Kim, Eun-Kyoung]
DGIST Authors
Lee, J[Lee, Jaemeun]; Kim, K[Kim, Kyungchan]; Yu, SW[Yu, Seong-Woon]Kim, EK[Kim, Eun-Kyoung]
Issue Date
2016-03-08
Citation
Molecular Brain, 9
Type
Article
Article Type
Article
Keywords
Brain-Derived InsulinHypothalamusNeuroD1Wnt/Beta-Catenin Signaling
ISSN
1756-6606
Abstract
Background: Insulin 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. Results: Here, 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. Conclusion: Taken 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.
URI
http://hdl.handle.net/20.500.11750/2291
DOI
10.1186/s13041-016-0207-5
Publisher
BioMed Central Ltd.
Related Researcher
Files:
There are no files associated with this item.
Collection:
Brain and Cognitive SciencesLaboratory of Neuronal Cell Death1. Journal Articles


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