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垂直袖子胃切除术通过FGF15/19/19通过增强β细胞功能和生存来改善葡萄糖-胰岛素稳态

Gabriela M Soares¹, Sandra L Balbo^1,2, Gabriela A Bronczek¹

¹Obesity and Comorbidities Research Center (OCRC), Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil.

American journal of physiology. Endocrinology and metabolism

|December 20, 2023

概括

垂直袖子胃切除术 (VSG) 通过减少胰腺小岛功能障碍,改善肥胖患者的葡萄糖控制. 这种效应是由纤维细胞生长因子 (FGF) 15/19增加的介导,它可以保护小岛免受压力和炎症.

科学领域:

代谢手术是一种代谢手术.
内分泌学在内分泌学.
肥胖研究的研究.

背景情况:

垂直袖子胃切除术 (VSG) 改善了肥胖个体的葡萄糖平衡.
纤维细胞生长因子 (FGF) 15/19水平在VSG后升高与改善的代谢功能有关.
关于FGF15/19对肥胖的胰腺小岛的具体影响仍然不完全理解.

研究的目的:

在饮食诱导的肥胖小鼠模型中研究VSG对胰腺小岛功能的影响.
确定FGF15/19在调解VSG对小岛形态和功能有益影响中的作用.
阐明FGF15/19影响小岛细胞应激,炎症和生存的机制.

主要方法:

在小鼠中饮食诱导的肥胖模型.
在VSG后评估胰腺小岛形态,β细胞和α细胞质量.
在岛屿中测量内质网膜 (ER) 压力和炎症标志物的基因表达.
在体外研究中,使用INS-1Eβ细胞治疗肥胖和VSG治疗小鼠的血清.
药理上抑制FGF受体 (FGFR) 信号传递.
管理复合FGF19.9的管理.

主要成果:

在肥胖小鼠中,VSG减弱了胰岛素过分分泌和减少了岛屿,β细胞和α细胞质量.
在胰腺小岛中,VSG降低了ER压力和炎症标志物.
接受VSG治疗的小鼠血清保护了INS-1Eβ细胞免受肥胖小鼠血清诱导的功能障碍和亡.
VSG增加了循环FGF15水平,并在小岛和β细胞中调节了FGFR1和β-klotho的表达.
抑制FGFR阻断了VSG血清的保护作用,而复合FGF19则提供了保护.

结论:

在肥胖症中,VSG可以改善胰腺小岛功能障碍,部分是通过FGF15/19信号传递.
FGF15/19在减少ER压力,炎症和VSG后胰腺小岛的亡方面发挥着至关重要的作用.
准FGF15/19通路代表了一种潜在的治疗策略,用于恢复肥胖的小岛功能.

关键词:

减肥手术减肥手术是什么纤维细胞生长因子 15/19/19 胰岛素分泌的胰岛素分泌.肥胖肥胖肥胖肥胖肥胖肥胖肥胖肥胖胰腺小岛的功能

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