葡萄糖-FGF21轴在改善葡萄糖不耐受和SGLT2抑制期间的β细胞功能中的作用
Maria Moreno-Lopez1, Isaline Louvet1, Nathalie Delalleau1
1Univ. Lille, CHU Lille, Inserm U1190, EGID, Institut Pasteur de Lille, Lille, France.
Diabetes, obesity & metabolism
|December 2, 2024
概括
纤维细胞生长因子21 (FGF21) 增强胰腺功能,并增强SGLT2抑制的益处. 这种相互作用是改善2型糖尿病和糖尿病前期糖尿病的葡萄糖和脂质代谢的关键.
科学领域:
- 内分泌学 在内分泌学.
- 代谢研究研究 代谢研究
- 分子生物学分子生物学
背景情况:
- 纤维细胞生长因子21 (FGF21),主要是一种肝激素,也在胰腺中表达,但其作用尚不清楚.
- -葡萄糖共运输体2抑制剂 (SGLT2i) 改善葡萄糖和脂质代谢,但潜在的机制,特别是葡萄糖-FGF21轴的参与,需要进一步研究.
研究的目的:
- 为了研究葡萄糖-FGF21相互作用在SGLT2抑制的代谢作用中的作用.
- 确定这种相互作用是否对提高葡萄糖不耐受或2型糖尿病 (T2D) 患者的葡萄糖和脂质代谢至关重要.
主要方法:
- 在人类胰腺组织中使用RNAscope,qPCR和免疫光学分析FGF21,FGF1R和β-klotho表达.
- 评估使用重组FGF21 (rFGF21) 的葡萄糖刺激胰岛素分泌 (GSIS) 在来自葡萄糖不耐受或T2D的捐赠者的小岛上.
- 使用野生型 (WT) 和Sglt2淘汰赛 (KO) 的小鼠在或高脂肪饮食中,用载体或达帕格利弗洛辛治疗,以研究SGLT2i中葡萄糖-FGF21轴的益处.
主要成果:
- 慢性rFGF21治疗改善了葡萄糖不耐受性捐赠者的岛屿中的GSIS,与增加的FGFR1表达相关.
- 在饮食诱导的抗胰岛素小鼠中,达帕格利弗洛辛治疗降低了食后葡萄糖,增加了血葡萄糖和FGF21.
- 在Sglt2 KO小鼠中,禁食时葡萄糖水平升高,在饮食诱导的胰岛素抵抗性Sglt2 KO小鼠中,葡萄糖和FGF21治疗效果升高.
结论:
- FGF21在肝胰沟通中起到至关重要的调解作用,增强葡萄糖和脂质代谢.
- FGF21改善胰腺功能,并放大SGLT2抑制剂的治疗效果.
- 葡萄糖-FGF21轴为糖尿病前期和2型糖尿病管理提供了潜在的治疗标.
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