Zhx2 maintains islet β-cell mass and function by transcriptionally regulating Pax6
Emerging evidence shows that pancreatic β-cell function and quality are key determinants in the progression of type 2 diabetes (T2D). The transcription factor zinc finger homeobox 2 (Zhx2) is involved in proliferation and development of multiple cells. However, the exact role of Zhx2 in β-cells and...
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Veröffentlicht in: | iScience 2023-06, Vol.26 (6), p.106871-106871, Article 106871 |
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Sprache: | eng |
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Zusammenfassung: | Emerging evidence shows that pancreatic β-cell function and quality are key determinants in the progression of type 2 diabetes (T2D). The transcription factor zinc finger homeobox 2 (Zhx2) is involved in proliferation and development of multiple cells. However, the exact role of Zhx2 in β-cells and T2D remains completely unknown. Here, we report that Zhx2 orchestrates β-cell mass and function by regulating paired box protein pax-6 (Pax6). We found that β-cell-specific knockout Zhx2 (Zhx2BKO) mice showed a decrease in β-cell proliferation and glucose homeostasis. Under prediabetic and diabetic conditions, we discovered glucose intolerance in both Zhx2BKO-HFD mice and Zhx2BKO-db/db mice, with reduced β-cell mass and insulin secretion. Mechanistically, we demonstrated that Zhx2 targeted the Pax6 promoter region (−1740∼-1563; −862∼-559; −251∼+75), enhanced promoter activity. Overall, Zhx2 maintains β-cell function by transcriptionally regulating Pax6, which provides a therapeutic target for diabetes intervention.
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•Zhx2 deletion in islet β-cells impairs glucose homeostasis in vivo•Zhx2 promotes β-cell proliferation and insulin secretion•Zhx2 maintains β-cell function by transcriptionally regulating Pax6
Molecular biology; Endocrinology; Model organism |
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ISSN: | 2589-0042 2589-0042 |
DOI: | 10.1016/j.isci.2023.106871 |