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J Biol Chem. 2018 Feb 9;293(6):2053-2065. doi: 10.1074/jbc.M117.809582. Epub 2017 Dec 19.

Hepatitis B X-interacting protein promotes the formation of the insulin gene-transcribing protein complex Pdx-1/Neurod1 in animal pancreatic β-cells.

Author information

1
From the State Key Laboratory of Medicinal Chemical Biology, Departments of Biochemistry and.
2
Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, China.
3
From the State Key Laboratory of Medicinal Chemical Biology, Departments of Biochemistry and zhwybao@nankai.edu.cn.
4
From the State Key Laboratory of Medicinal Chemical Biology, Departments of Biochemistry and yelihong@nankai.edu.cn.

Abstract

The activation of insulin gene transcription depends on multiple nuclear proteins, including the transcription factors PDX-1 and NEUROD1, which form a transcriptional complex. We recently reported that hepatitis B X-interacting protein (HBXIP, also termed LAMTOR5) can modulate glucose metabolism reprogramming in cancer cells. However, the physiological role of HBXIP in the modulation of glucose metabolism in normal tissues is poorly understood. Here, we report that Hbxip is an essential regulator of the effect of the Pdx-1/Neurod1 complex on insulin gene transcription in murine pancreatic β-cells in vitro and in vivo We found that pancreatic β-cell-specific Hbxip-knockout mice displayed higher fasting blood glucose levels and impaired glucose tolerance. Furthermore, Hbxip was involved in the regulation of insulin in the pancreas islets and increased insulin gene expression in rat pancreatic β-cells. Mechanistically, Hbxip stimulated insulin enhancer activity by interacting with Pdx-1 and recruiting Neurod1 to Pdx-1. Functionally, we provide evidence that Hbxip is required for Pdx-1/Neurod1-mediated insulin expression in rat pancreatic β-cells. Collectively, these results indicate that Hbxip is involved in the transcription of insulin by increasing the levels of the Pdx-1/Neurod1 complex in animal pancreatic β-cells. Our finding provides the insight into the mechanism by which Hbxip stimulates the transcription of the insulin gene.

KEYWORDS:

HBXIP; Neurod1; PDX-1; glucose; insulin; pancreas; transcription co-activator; transcription regulation; β cell

PMID:
29259128
PMCID:
PMC5808766
DOI:
10.1074/jbc.M117.809582
[Indexed for MEDLINE]
Free PMC Article

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