Follicle-stimulating hormone orchestrates glucose-stimulated insulin secretion of pancreatic islets.
Follicle-stimulating hormone orchestrates glucose-stimulated insulin secretion of pancreatic islets.
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DOI：
10.1038/s41467-023-42801-6
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发表时间：
2023-11-01
影响因子：
16.6
通讯作者：
Huang, He-Feng
中科院分区：
文献类型：
--
作者：
Cheng, Yi;Zhu, Hong;Ren, Jun;Wu, Hai-Yan;Yu, Jia-En;Jin, Lu-Yang;Pang, Hai-Yan;Pan, Hai-Tao;Luo, Si-Si;Yan, Jing;Dong, Kai-Xuan;Ye, Long-Yun;Zhou, Cheng-Liang;Pan, Jie-Xue;Meng, Zhuo-Xian;Yu, Ting;Jin, Li;Lin, Xian-Hua;Wu, Yan-Ting;Yang, Hong-Bo;Liu, Xin-Mei;Sheng, Jian-Zhong;Ding, Guo-Lian;Huang, He-Feng
促卵泡激素（FSH）通过与FSH受体（FSHR）结合参与哺乳动物的生殖。然而，一些研究发现FSH和FSHR在性腺外组织中发挥重要作用。在此，我们鉴定了人和小鼠胰岛β细胞中FSHR的表达。通过Fshr敲除阻断FSH信号传导导致葡萄糖耐量受损，这是由于胰岛素分泌减少，而高FSH水平也导致胰岛素分泌不足。在体外，我们发现FSH以钟形曲线的方式协调葡萄糖刺激的胰岛素分泌（GSIS）。FSH主要通过FSHR激活Gαs，促进cAMP/蛋白激酶A（PKA）和钙离子通道，从而刺激GSIS，而高FSH水平则激活Gαi，抑制cAMP/PKA通道，从而抑制GSIS的放大效应。我们的研究结果揭示了FSH在调节胰岛胰岛素分泌中的作用，并为未来绝经后糖尿病的临床研究和治疗策略提供了途径。促卵泡激素（FSH）参与哺乳动物的生殖，但一些研究表明FSH及其受体在性腺外组织中发挥作用。在这里，作者表明FSH通过其在胰腺β细胞上的受体协调葡萄糖刺激的胰岛素分泌（GSIS），绝经前FSH水平剂量依赖性地促进GSIS，绝经后FSH水平抑制这种作用。
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. Follicle-stimulating hormone (FSH) is involved in mammalian reproduction, but several studies have suggested a role of FSH and its receptor in extragonadal tissue. Here, the authors show that FSH orchestrates glucose-stimulated insulin secretion (GSIS) via its receptor on pancreatic β-cells, with pre-menopausal FSH levels dose-dependently promoting GSIS and postmenopausal FSH levels inhibiting this effect.
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