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

Cell metabolism 2023 Jun 06

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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 sustained 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 restores the percentage of GI neurons in db/db mice. Importantly, intranasal delivery of FGF4 alleviates hyperglycemia 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. Copyright © 2023 Elsevier Inc. All rights reserved.

Citation

Hongbin Sun, Wei Lin, Yu Tang, Hongqing Tu, Ting Chen, Jie Zhou, Dezhong Wang, Qingqing Xu, Jianlou Niu, Wenliya Dong, Sidan Liu, Xinyan Ni, Wen Yang, Yingzheng Zhao, Lei Ying, Jie Zhang, Xiaokun Li, Moosa Mohammadi, Wei L Shen, Zhifeng Huang. Sustained remission of type 2 diabetes in rodents by centrally administered fibroblast growth factor 4. Cell metabolism. 2023 Jun 06;35(6):1022-1037.e6