IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-35998-z.html
   My bibliography  Save this article

Circular RNA circGlis3 protects against islet β-cell dysfunction and apoptosis in obesity

Author

Listed:
  • Yue Liu

    (School of life Science and Technology, China Pharmaceutical University)

  • Yue Yang

    (School of life Science and Technology, China Pharmaceutical University)

  • Chenying Xu

    (School of life Science and Technology, China Pharmaceutical University)

  • Jianxing Liu

    (School of life Science and Technology, China Pharmaceutical University)

  • Jiale Chen

    (School of life Science and Technology, China Pharmaceutical University)

  • Guoqing Li

    (Zhongda Hospital, School of Medicine, Southeast University)

  • Bin Huang

    (School of life Science and Technology, China Pharmaceutical University)

  • Yi Pan

    (School of life Science and Technology, China Pharmaceutical University)

  • Yanfeng Zhang

    (School of life Science and Technology, China Pharmaceutical University)

  • Qiong Wei

    (Zhongda Hospital, School of Medicine, Southeast University)

  • Stephen J. Pandol

    (Cedars-Sinai Medical Center)

  • Fangfang Zhang

    (School of life Science and Technology, China Pharmaceutical University)

  • Ling Li

    (Zhongda Hospital, School of Medicine, Southeast University)

  • Liang Jin

    (School of life Science and Technology, China Pharmaceutical University)

Abstract

Pancreatic β-cell compensation is a major mechanism in delaying T2DM progression. Here we report the abnormal high expression of circGlis3 in islets of male mice with obesity and serum of people with obesity. Increasing circGlis3 is regulated by Quaking (QKI)-mediated splicing circularization. circGlis3 overexpression enhances insulin secretion and inhibits obesity-induced apoptosis in vitro and in vivo. Mechanistically, circGlis3 promotes insulin secretion by up-regulating NeuroD1 and Creb1 via sponging miR-124-3p and decreases apoptosis via interacting with the pro-apoptotic factor SCOTIN. The RNA binding protein FUS recruits circGlis3 and collectively assemble abnormal stable cytoplasmic stress granules (SG) in response to cellular stress. These findings highlight a physiological role for circRNAs in β-cell compensation and indicate that modulation of circGlis3 expression may represent a potential strategy to prevent β-cell dysfunction and apoptosis after obesity.

Suggested Citation

  • Yue Liu & Yue Yang & Chenying Xu & Jianxing Liu & Jiale Chen & Guoqing Li & Bin Huang & Yi Pan & Yanfeng Zhang & Qiong Wei & Stephen J. Pandol & Fangfang Zhang & Ling Li & Liang Jin, 2023. "Circular RNA circGlis3 protects against islet β-cell dysfunction and apoptosis in obesity," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35998-z
    DOI: 10.1038/s41467-023-35998-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-35998-z
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-35998-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Stephan Herzig & Fanxin Long & Ulupi S. Jhala & Susan Hedrick & Rebecca Quinn & Anton Bauer & Dorothea Rudolph & Gunther Schutz & Cliff Yoon & Pere Puigserver & Bruce Spiegelman & Marc Montminy, 2001. "Correction: CREB regulates hepatic gluconeogenesis through the coactivator PGC-1," Nature, Nature, vol. 413(6856), pages 652-652, October.
    2. Sebastian Memczak & Marvin Jens & Antigoni Elefsinioti & Francesca Torti & Janna Krueger & Agnieszka Rybak & Luisa Maier & Sebastian D. Mackowiak & Lea H. Gregersen & Mathias Munschauer & Alexander Lo, 2013. "Circular RNAs are a large class of animal RNAs with regulatory potency," Nature, Nature, vol. 495(7441), pages 333-338, March.
    3. Lisa Stoll & Adriana Rodríguez-Trejo & Claudiane Guay & Flora Brozzi & Mustafa Bilal Bayazit & Sonia Gattesco & Véronique Menoud & Jonathan Sobel & Ana Claudia Marques & Morten Trillingsgaard Venø & J, 2020. "A circular RNA generated from an intron of the insulin gene controls insulin secretion," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    4. Justin W. Chartron & Katherine C. L. Hunt & Judith Frydman, 2016. "Cotranslational signal-independent SRP preloading during membrane targeting," Nature, Nature, vol. 536(7615), pages 224-228, August.
    5. Sadaf Amin & Brandoch Cook & Ting Zhou & Zaniar Ghazizadeh & Raphael Lis & Tuo Zhang & Mona Khalaj & Miguel Crespo & Manuradhi Perera & Jenny Zhaoying Xiang & Zengrong Zhu & Mark Tomishima & Chengyang, 2018. "Discovery of a drug candidate for GLIS3-associated diabetes," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    6. Fangfang Zhang & Dongshen Ma & Wanli Zhao & Danwei Wang & Tingsheng Liu & Yuhong Liu & Yue Yang & Yue Liu & Jinming Mu & Bingbing Li & Yanfeng Zhang & Yi Pan & Changying Guo & Hong Du & Ling Li & Xian, 2020. "Obesity-induced overexpression of miR-802 impairs insulin transcription and secretion," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    7. Fangfang Zhang & Yue Yang & Xi Chen & Yue Liu & Qianxing Hu & Bin Huang & Yuhong Liu & Yi Pan & Yanfeng Zhang & Dechen Liu & Rui Liang & Guoqing Li & Qiong Wei & Ling Li & Liang Jin, 2021. "The long non-coding RNA βFaar regulates islet β-cell function and survival during obesity in mice," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    8. Stephan Herzig & Fanxin Long & Ulupi S. Jhala & Susan Hedrick & Rebecca Quinn & Anton Bauer & Dorothea Rudolph & Gunther Schutz & Cliff Yoon & Pere Puigserver & Bruce Spiegelman & Marc Montminy, 2001. "CREB regulates hepatic gluconeogenesis through the coactivator PGC-1," Nature, Nature, vol. 413(6852), pages 179-183, September.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yuta Ozaki & Koji Ohashi & Naoya Otaka & Hiroshi Kawanishi & Tomonobu Takikawa & Lixin Fang & Kunihiko Takahara & Minako Tatsumi & Sohta Ishihama & Mikito Takefuji & Katsuhiro Kato & Yuuki Shimizu & Y, 2023. "Myonectin protects against skeletal muscle dysfunction in male mice through activation of AMPK/PGC1α pathway," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Storm N. S. Reid & Joung-Hyun Park & Yunsook Kim & Yi Sub Kwak & Byeong Hwan Jeon, 2020. "In Vitro and In Vivo Effects of Fermented Oyster-Derived Lactate on Exercise Endurance Indicators in Mice," IJERPH, MDPI, vol. 17(23), pages 1-17, November.
    3. Simeon R. Mihaylov & Lydia M. Castelli & Ya-Hui Lin & Aytac Gül & Nikita Soni & Christopher Hastings & Helen R. Flynn & Oana Păun & Mark J. Dickman & Ambrosius P. Snijders & Robert Goldstone & Oliver, 2023. "The master energy homeostasis regulator PGC-1α exhibits an mRNA nuclear export function," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    4. Pengfei Xu & Yingjie Zhang & Xinghao Jiang & Junyan Li & Liying Song & Mir Hasson Khoso & Yunye Liu & Qiang Wu & Guiping Ren & Deshan Li, 2016. "Canine Fibroblast Growth Factor 21 Ameliorates Hyperglycemia Associated with Inhibiting Hepatic Gluconeogenesis and Improving Pancreatic Beta-Cell Survival in Diabetic Mice and Dogs," PLOS ONE, Public Library of Science, vol. 11(5), pages 1-19, May.
    5. Ewa Bielczyk-Maczynska & Meng Zhao & Peter-James H. Zushin & Theresia M. Schnurr & Hyun-Jung Kim & Jiehan Li & Pratima Nallagatla & Panjamaporn Sangwung & Chong Y. Park & Cameron Cornn & Andreas Stahl, 2022. "G protein-coupled receptor 151 regulates glucose metabolism and hepatic gluconeogenesis," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Junliang Yin & Xiaowen Han & Yongxing Zhu & Zhengwu Fang & Derong Gao & Dongfang Ma, 2022. "Transcriptome Profiles of Circular RNAs in Common Wheat during Fusarium Head Blight Disease," Data, MDPI, vol. 7(9), pages 1-8, August.
    7. Yu Dong & Qian Gao & Yong Chen & Zhao Zhang & Yanhua Du & Yuan Liu & Guangxiong Zhang & Shengli Li & Gaoyang Wang & Xiang Chen & Hong Liu & Leng Han & Youqiong Ye, 2023. "Identification of CircRNA signature associated with tumor immune infiltration to predict therapeutic efficacy of immunotherapy," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Mi-Young Song & Chang Yeob Han & Young Jae Moon & Ju Hyung Lee & Eun Ju Bae & Byung-Hyun Park, 2022. "Sirt6 reprograms myofibers to oxidative type through CREB-dependent Sox6 suppression," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    9. Jordan Currie & Vyshnavi Manda & Sean K. Robinson & Celine Lai & Vertica Agnihotri & Veronica Hidalgo & R. W. Ludwig & Kai Zhang & Jay Pavelka & Zhao V. Wang & June-Wha Rhee & Maggie P. Y. Lam & Edwar, 2024. "Simultaneous proteome localization and turnover analysis reveals spatiotemporal features of protein homeostasis disruptions," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    10. Amir Bar & Liron Argaman & Michal Eldar & Hanah Margalit, 2023. "TRS: a method for determining transcript termini from RNAtag-seq sequencing data," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    11. Sen Ma & Xiaochun Xu & Xiaolong Wang & Yuxin Yang & Yinghua Shi & Yulin Chen, 2022. "Comprehensive Profiling of Circular RNAs in Goat Dermal Papilla Cells and Prediction of Their Modulatory Roles in Hair Growth," Agriculture, MDPI, vol. 12(9), pages 1-14, August.
    12. Bin Li & Wen-Wu Bai & Tao Guo & Zhen-Yu Tang & Xue-Jiao Jing & Ti-Chao Shan & Sen Yin & Ying Li & Fu Wang & Mo-Li Zhu & Jun-Xiu Lu & Yong-Ping Bai & Bo Dong & Peng Li & Shuang-Xi Wang, 2024. "Statins improve cardiac endothelial function to prevent heart failure with preserved ejection fraction through upregulating circRNA-RBCK1," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    13. Nana Xu & Jiebang Jiang & Fei Jiang & Guokai Dong & Li Meng & Meng Wang & Jing Chen & Cong Li & Yongping Shi & Sisi He & Rongpeng Li, 2024. "CircCDC42-encoded CDC42-165aa regulates macrophage pyroptosis in Klebsiella pneumoniae infection through Pyrin inflammasome activation," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    14. Xiaojie Ma & Jie Cao & Ziyu Zhou & Yunkun Lu & Qin Li & Yan Jin & Guo Chen & Weiyun Wang & Wenyan Ge & Xi Chen & Zhensheng Hu & Xiao Shu & Qian Deng & Jiaqi Pu & Chengzhen Liang & Junfen Fu & Jianzhao, 2022. "N6-methyladenosine modification-mediated mRNA metabolism is essential for human pancreatic lineage specification and islet organogenesis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    15. Ting-Ting He & Yun-Fan Xu & Xiang Li & Xia Wang & Jie-Yu Li & Dan Ou-Yang & Han-Sen Cheng & Hao-Yang Li & Jia Qin & Yu Huang & Hai-Yan Wang, 2023. "A linear and circular dual-conformation noncoding RNA involved in oxidative stress tolerance in Bacillus altitudinis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    16. Xianjun Dong & Yunfei Bai & Zhixiang Liao & David Gritsch & Xiaoli Liu & Tao Wang & Rebeca Borges-Monroy & Alyssa Ehrlich & Geidy E. Serrano & Mel B. Feany & Thomas G. Beach & Clemens R. Scherzer, 2023. "Circular RNAs in the human brain are tailored to neuron identity and neuropsychiatric disease," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    17. Ulrike Zinnall & Miha Milek & Igor Minia & Carlos H. Vieira-Vieira & Simon Müller & Guido Mastrobuoni & Orsalia-Georgia Hazapis & Simone Giudice & David Schwefel & Nadine Bley & Franka Voigt & Jeffrey, 2022. "HDLBP binds ER-targeted mRNAs by multivalent interactions to promote protein synthesis of transmembrane and secreted proteins," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    18. Mateja Rybiczka-Tešulov & Oxana Garritsen & Morten T. Venø & Laura Wieg & Roland van Dijk & Karim Rahimi & Andreia Gomes-Duarte & Marina de Wit & Lieke L. Haar & Lars Michels & Nicky C. H. van Kronenb, 2024. "Circular RNAs regulate neuron size and migration of midbrain dopamine neurons during development," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    19. Roberta Piras & Emily Y. Ko & Connor Barrett & Marco Simone & Xianzhi Lin & Marina T. Broz & Fernando H. G. Tessaro & Mireia Castillo-Martin & Carlos Cordon-Cardo & Helen S. Goodridge & Dolores Vizio , 2022. "circCsnk1g3- and circAnkib1-regulated interferon responses in sarcoma promote tumorigenesis by shaping the immune microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    20. Shaomin Yang & Di Cao & Dabbu Kumar Jaijyan & Mei Wang & Jian Liu & Ruth Cruz-cosme & Songbin Wu & Jiabin Huang & Mulan Zeng & Xiaolian Liu & Wuping Sun & Donglin Xiong & Qiyi Tang & Lizu Xiao & Hua Z, 2024. "Identification and characterization of Varicella Zoster Virus circular RNA in lytic infection," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35998-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.