Cited time in webofscience Cited time in scopus

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

Wnt3a upregulates brain-derived insulin by increasing NeuroD1 via Wnt/beta-catenin signaling in the hypothalamus
Lee, JaemeunKim, KyungchanYu, Seong-WoonKim, Eun-Kyoung
DGIST Authors
Yu, Seong-WoonKim, Eun-Kyoung
Issued Date
Article Type
Brain-Derived InsulinHypothalamusNeuroD1Wnt/Beta-Catenin Signaling
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.
BioMed Central Ltd.
Related Researcher
  • 유성운 Yu, Seong-Woon 뇌과학과
  • Research Interests Molecular mechanisms of neuronal cell death and neurodegeneration
Files in This Item:


기타 데이터 / 2.44 MB / Adobe PDF download
Appears in Collections:
Department of Brain Sciences Lab of Neuro-Metabolism & Neurometabolomic Research Center 1. Journal Articles
Department of Brain Sciences Laboratory of Neuronal Cell Death 1. Journal Articles


  • twitter
  • facebook
  • mendeley

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.