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Year:: 2024
Contributor:: Morka, Angela (Author); Landa Galvan, Huguet (Author); Castro, Thalia (Author); Alonso, Laura (Author)
Subject:: diabetes; Medicine; Metabolism; cell biology; Molecular Biology; endocrinology
DOI: https://doi.org/10.26300/5882-fh56

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Abstract:: Type 2 Diabetes (T2D) is caused by a deficiency in mass or function of beta cells in pancreatic islets, leading to failure to meet insulin demand. A previous study aimed to increase beta cell mass and proliferation through activation of the ATF6 pathway of the Unfolded Protein Response, which in high glucose conditions significantly increases beta cell proliferation. Preliminary CUT&RUN sequencing data showed potential direct binding of ATF6 to the Zfp367 promoter. Zfp367 is known to promote proliferation and tumorigenesis in a variety of cancers. In contrast, there is also evidence to support the opposite biological function of Zfp367 in blocking proliferation in cancer cell lines and during neurogenesis. However, the role of Zfp367 on beta cell proliferation induced by ATF6 is unknown. To explore the role of Zfp367, we transduced mouse islet cells with various adenoviruses and shRNAs to understand the impact of overexpressing and knocking down Zfp367 on ATF6-mediated beta cell proliferation in high glucose conditions. We evaluated transcriptional markers of proliferation and transcriptional targets of ATF6 by qPCR. We also assessed beta cell proliferation by BrdU uptake assays, quantifying the percentage of BrdU+/Insulin+ cells by immunostaining. Further implications of confirming the role of Zfp367 include developing potential therapeutics for T2D that target Zfp367.

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Morka, Angela, Landa Galvan, Huguet, Castro, Thalia, et al., "Role of ZFP367 in ATF6-Induced Beta Cell Proliferation" (2024). The Leadership Alliance Digital Library, Summer Research Symposium. Brown Digital Repository. Brown University Library. https://doi.org/10.26300/5882-fh56

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The Leadership Alliance Digital Library

A collection of research presentations and posters created by students participating in the Leadership Alliance's Summer Research - Early Identification Program.
When using this resource, please cite the digital object identifier (DOI) for the specific resource as well as the …

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Summer Research Symposium

Each year, Brown University showcases the research of its undergraduates at the Summer Research Symposium. More than half of the student-researchers are UTRA recipients, while others receive funding from a variety of Brown-administered and national programs and fellowships and go …
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Role of ZFP367 in ATF6-Induced Beta Cell Proliferation