小柯机器人

温州医科大学Zhifeng Huang和上海科技大学Wei L. Shen共同合作，近期取得重要工作进展。他们研究提出了中枢给药成纤维细胞生长因子4（icvFGF4）对啮齿类动物2型糖尿病的持续缓解。相关研究成果2023年5月10日在线发表于《细胞—代谢》杂志上。

据介绍，2型糖尿病（T2D）是世界范围内的主要健康和经济负担。尽管有多种药物可用于短期治疗，但T2D的持续缓解目前在药理学上是无法实现的。成纤维细胞生长因子1（icvFGF1）的脑室内给药诱导T2D啮齿动物的持续缓解，推动了人们深入研究其作用机制。目前尚不清楚其他FGF是否具有类似的治疗效果。

研究人员发现icvFGF4还通过激活下丘脑中基底部葡萄糖感应神经元中表达的FGF受体1（FGFR1），在雄性db/db小鼠和饮食诱导的肥胖小鼠中引发持续的抗糖尿病作用。具体而言，FGF4刺激葡萄糖兴奋（GE）神经元，同时抑制葡萄糖抑制（GI）神经元。

此外，icvFGF4可恢复db/db小鼠胃肠道神经元的百分比。FGF4的鼻内递送缓解了db/db小鼠的高血糖，为非侵入性治疗提供了基础。

总之，研究表明，icvFGF4在实现T2D持续缓解方面具有显著的治疗潜力。

附：英文原文

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

Author: 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

Issue&Volume: 2023-05-10

Abstract: Type 2 diabetes (T2D) is a major health and economic burden worldwide. Despite theavailability of multiple drugs for short-term management, sustained remission of T2Dis currently not achievable pharmacologically. Intracerebroventricular administrationof fibroblast growth factor 1 (icvFGF1) induces sustained remission in T2D rodents,propelling intense research efforts to understand its mechanism of action. Whetherother FGFs possess similar therapeutic benefits is currently unknown. Here, we showthat 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 inglucose-sensing neurons within the mediobasal hypothalamus. Specifically, FGF4 excitesglucose-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 significanttherapeutic potential for achieving sustained remission of T2D.

DOI: 10.1016/j.cmet.2023.04.018

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00172-9

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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