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Follicle-stimulating hormone orchestrates glucose-stimulated insulin secretion of pancreatic islets

Author

Listed:
  • Yi Cheng

    (Fudan University
    Chinese Academy of Medical Sciences
    Zhejiang University School of Medicine)

  • Hong Zhu

    (Fudan University
    Chinese Academy of Medical Sciences)

  • Jun Ren

    (Zhejiang University School of Medicine)

  • Hai-Yan Wu

    (Zhejiang University School of Medicine)

  • Jia-En Yu

    (Zhejiang University School of Medicine)

  • Lu-Yang Jin

    (Zhejiang University School of Medicine)

  • Hai-Yan Pang

    (Zhejiang University School of Medicine)

  • Hai-Tao Pan

    (Shaoxing Maternity and Child Health Care Hospital
    Shanghai Jiao Tong University)

  • Si-Si Luo

    (Shanghai Jiao Tong University
    Shanghai Key Laboratory of Embryo Original Diseases)

  • Jing Yan

    (Fudan University
    Chinese Academy of Medical Sciences)

  • Kai-Xuan Dong

    (Chinese Academy of Medical Sciences
    Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Long-Yun Ye

    (Fudan University Shanghai Cancer Centre)

  • Cheng-Liang Zhou

    (Shanghai Jiao Tong University
    Shanghai Key Laboratory of Embryo Original Diseases)

  • Jie-Xue Pan

    (Fudan University
    Chinese Academy of Medical Sciences)

  • Zhuo-Xian Meng

    (Zhejiang University School of Medicine)

  • Ting Yu

    (Zhejiang University School of Medicine)

  • Li Jin

    (Fudan University
    Chinese Academy of Medical Sciences)

  • Xian-Hua Lin

    (Fudan University
    Chinese Academy of Medical Sciences)

  • Yan-Ting Wu

    (Fudan University
    Chinese Academy of Medical Sciences)

  • Hong-Bo Yang

    (Fudan University
    Chinese Academy of Medical Sciences)

  • Xin-Mei Liu

    (Fudan University
    Chinese Academy of Medical Sciences)

  • Jian-Zhong Sheng

    (Fudan University
    Chinese Academy of Medical Sciences
    Zhejiang University School of Medicine
    the Fourth Affiliated Hospital of Zhejiang University School of Medicine)

  • Guo-Lian Ding

    (Fudan University
    Chinese Academy of Medical Sciences)

  • He-Feng Huang

    (Fudan University
    Chinese Academy of Medical Sciences
    Zhejiang University School of Medicine
    Shanghai Key Laboratory of Embryo Original Diseases)

Abstract

Follicle-stimulating hormone (FSH) is involved in mammalian reproduction via binding to FSH receptor (FSHR). However, several studies have found that FSH and FSHR play important roles in extragonadal tissue. Here, we identified the expression of FSHR in human and mouse pancreatic islet β-cells. Blocking FSH signaling by Fshr knock-out led to impaired glucose tolerance owing to decreased insulin secretion, while high FSH levels caused insufficient insulin secretion as well. In vitro, we found that FSH orchestrated glucose-stimulated insulin secretion (GSIS) in a bell curve manner. Mechanistically, FSH primarily activates Gαs via FSHR, promoting the cAMP/protein kinase A (PKA) and calcium pathways to stimulate GSIS, whereas high FSH levels could activate Gαi to inhibit the cAMP/PKA pathway and the amplified effect on GSIS. Our results reveal the role of FSH in regulating pancreatic islet insulin secretion and provide avenues for future clinical investigation and therapeutic strategies for postmenopausal diabetes.

Suggested Citation

  • Yi Cheng & Hong Zhu & Jun Ren & Hai-Yan Wu & Jia-En Yu & Lu-Yang Jin & Hai-Yan Pang & Hai-Tao Pan & Si-Si Luo & Jing Yan & Kai-Xuan Dong & Long-Yun Ye & Cheng-Liang Zhou & Jie-Xue Pan & Zhuo-Xian Meng, 2023. "Follicle-stimulating hormone orchestrates glucose-stimulated insulin secretion of pancreatic islets," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42801-6
    DOI: 10.1038/s41467-023-42801-6
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