Sustained remission of type 2 diabetes in rodents by centrally administered fibroblast growth factor 4

作者全名："Sun, Hongbin; Lin, Wei; Tang, Yu; Tu, Hongqing; Chen, Ting; Zhou, Jie; Wang, Dezhong; Xu, Qingqing; Niu, Jianlou; Dong, Wenliya; Liu, Sidan; Ni, Xinyan; Yang, Wen; Zhao, Yingzheng; Ying, Lei; Zhang, Jie; Li, Xiaokun; Mohammadi, Moosa; Shen, Wei L.; Huang, Zhifeng"

作者地址："[Sun, Hongbin; Tu, Hongqing; Chen, Ting; Ni, Xinyan; Yang, Wen; Shen, Wei L.] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China; [Sun, Hongbin; Tu, Hongqing; Chen, Ting; Ni, Xinyan; Yang, Wen; Shen, Wei L.] ShanghaiTech Univ, Shanghai Clin Res & Trial Ctr, Shanghai 201210, Peoples R China; [Lin, Wei; Tang, Yu; Zhou, Jie; Wang, Dezhong; Niu, Jianlou; Dong, Wenliya; Liu, Sidan; Zhao, Yingzheng; Ying, Lei; Li, Xiaokun; Mohammadi, Moosa; Huang, Zhifeng] Wenzhou Med Univ, Oujiang Lab, Zhejiang Lab Regenerat Med Vis & Brain Hlth, Wenzhou 325035, Zhejiang, Peoples R China; [Lin, Wei; Zhou, Jie; Wang, Dezhong; Niu, Jianlou; Dong, Wenliya; Liu, Sidan; Zhao, Yingzheng; Ying, Lei; Li, Xiaokun; Mohammadi, Moosa; Huang, Zhifeng] Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou 325035, Zhejiang, Peoples R China; [Tang, Yu; Zhang, Jie] Chengdu Med Coll, Sichuan Higher Educ Inst, Dept Physiol, Key Lab Thermoregulat & Inflammat, Chengdu 610500, Sichuan, Peoples R China; [Xu, Qingqing] Chongqing Med Univ, Biol Sci Inst, Chongqing 400016, Peoples R China"

通信作者："Shen, WL (通讯作者)，ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China.; Shen, WL (通讯作者)，ShanghaiTech Univ, Shanghai Clin Res & Trial Ctr, Shanghai 201210, Peoples R China.; Huang, ZF (通讯作者)，Wenzhou Med Univ, Oujiang Lab, Zhejiang Lab Regenerat Med Vis & Brain Hlth, Wenzhou 325035, Zhejiang, Peoples R China.; Huang, ZF (通讯作者)，Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou 325035, Zhejiang, Peoples R China."

来源：CELL METABOLISM

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001019611600001

JCR分区：Q1

影响因子：27.7

年份：2023

卷号：35

期号：6

开始页：1022

结束页：+

文献类型：Article

关键词：　

摘要："Type 2 diabetes (T2D) is a major health and economic burden worldwide. Despite the availability of multiple drugs for short-term management, sustained remission of T2D is currently not achievable pharmacologically. Intracerebroventricular administration of fibroblast growth factor 1 (icvFGF1) induces sustained remission in T2D rodents, propelling intense research efforts to understand its mechanism of action. Whether other FGFs possess similar therapeutic benefits is currently unknown. Here, we show that icvFGF4 also elicits a sus-tained antidiabetic effect in both male db/db mice and diet-induced obese mice by activating FGF receptor 1 (FGFR1) expressed in glucose-sensing neurons within the mediobasal hypothalamus. Specifically, FGF4 excites glucose-excited (GE) neurons while inhibiting glucose-inhibited (GI) neurons. Moreover, icvFGF4 re-stores the percentage of GI neurons in db/db mice. Importantly, intranasal delivery of FGF4 alleviates hyper-glycemia in db/db mice, paving the way for non-invasive therapy. We conclude that icvFGF4 holds significant therapeutic potential for achieving sustained remission of T2D."

基金机构："National Natural Science Foundation of China [92057122, 81874323, 32122039, 91857104, 31900707]; National Key Ramp;D Program of China [2019YFA0801900]; Shanghai Government Fund [21JC1404900, 21XD1422700]; Kungpeng Plan Award; Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine at ShanghaiTech University; MICF; Oujiang Lab [OJQD2022007, OJQDSP202205]"

基金资助正文："This study was funded by the National Natural Science Foundation of China (92057122 and 81874323 to Z.H.; 32122039 and 91857104 to W.L.S.; and 31900707 to H.S.), the National Key R & amp;D Program of China (2019YFA0801900 to W.L.S.), the Shanghai Government Fund (21JC1404900 and 21XD1422700 to W.L.S.), the Startup Grant from Oujiang Lab (OJQD2022007 to M.M. and OJQDSP202205 to Z.H.), and the Kungpeng Plan Award (to M.M.) and the MICF and Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine at ShanghaiTech University."