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

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, Ting Yu, Li Jin, Xian-Hua Lin, Yan-Ting Wu, Hong-Bo Yang, Xin-Mei Liu, Jian-Zhong Sheng (), Guo-Lian Ding () and He-Feng Huang ()
Additional contact information
Yi Cheng: Fudan University
Hong Zhu: Fudan University
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
Si-Si Luo: Shanghai Jiao Tong University
Jing Yan: Fudan University
Kai-Xuan Dong: Chinese Academy of Medical Sciences
Long-Yun Ye: Fudan University Shanghai Cancer Centre
Cheng-Liang Zhou: Shanghai Jiao Tong University
Jie-Xue Pan: Fudan University
Zhuo-Xian Meng: Zhejiang University School of Medicine
Ting Yu: Zhejiang University School of Medicine
Li Jin: Fudan University
Xian-Hua Lin: Fudan University
Yan-Ting Wu: Fudan University
Hong-Bo Yang: Fudan University
Xin-Mei Liu: Fudan University
Jian-Zhong Sheng: Fudan University
Guo-Lian Ding: Fudan University
He-Feng Huang: Fudan University

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-42801-6

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