2. Academic Validation
  3. Excessive iron inhibits insulin secretion via perturbing transcriptional regulation of SYT7 by OGG1

Excessive iron inhibits insulin secretion via perturbing transcriptional regulation of SYT7 by OGG1

  • Cell Mol Life Sci. 2023 May 20;80(6):159. doi: 10.1007/s00018-023-04802-y.
Xingqi Zhao 1,  Ying Ma 1,  Munan Shi 1,  Miaoling Huang 1,  Jingyu Xin 1,  Shusheng Ci 2,  Meimei Chen 3,  Tao Jiang 4,  Zhigang Hu 1,  Lingfeng He 1,  Feiyan Pan 5,  Zhigang Guo 6
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China.
  • 2 School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, Jiangsu, China.
  • 3 Department of Endocrinology, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210000, Jiangsu, China.
  • 4 Department of Geriatrics, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210000, Jiangsu, China.
  • 5 Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China. panfeiyan@njnu.edu.cn.
  • 6 Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China. guo@njnu.edu.cn.
PMID: 37209177 DOI: 10.1007/s00018-023-04802-y
Abstract

Although iron overload is closely related to the occurrence of type 2 diabetes mellitus (T2DM), the specific mechanism is unclear. Here, we found that excessive iron inhibited the secretion of Insulin (INS) and impaired islet β cell function through downregulating Synaptotagmin 7 (SYT7) in iron overload model in vivo and in vitro. Our results further demonstrated that 8-oxoguanine DNA glycosylase (OGG1), a key protein in the DNA base excision repair, was an upstream regulator of SYT7. Interestingly, such regulation could be suppressed by excessive iron. Ogg1-null mice, iron overload mice and db/db mice exhibit reduced INS secretion, weakened β cell function and subsequently impaired glucose tolerance. Notably, SYT7 overexpression could rescue these phenotypes. Our data revealed an intrinsic mechanism by which excessive iron inhibits INS secretion through perturbing the transcriptional regulation of SYT7 by OGG1, which suggested that SYT7 was a potential target in clinical therapy for T2DM.

Keywords

Chronic degenerative disease; Gene transcription; Oxidative stress; Target therapy; Vesicle transport.

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