Mehl Florence, Sánchez-Archidona Ana Rodríguez, Meitil Ida, Gerl Mathias, Cruciani-Guglielmacci Céline, Wigger Leonore, Le Stunff Hervé, Meneyrol Kelly, Lallement Justine, Denom Jessica, Klose Christian, Simons Kai, Pagni Marco, Magnan Christophe, Ibberson Mark, Thorens Bernard
Vital-IT Group, SIB Swiss Institute for Bioinformatics, 1015 Lausanne, Switzerland.
Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland.
iScience. 2024 Oct 11;27(11):111134. doi: 10.1016/j.isci.2024.111134. eCollection 2024 Nov 15.
To identify the pathways that are coordinately regulated in pancreatic β cells, muscle, liver, and fat to control fasting glycemia we fed C57Bl/6, DBA/2, and Balb/c mice a regular chow or a high fat diet for 5, 13, and 33 days. Physiological, transcriptomic and lipidomic data were used in a data fusion approach to identify organ-specific pathways linked to fasting glycemia across all conditions investigated. In pancreatic islets, constant insulinemia despite higher glycemic levels was associated with reduced expression of hormone and neurotransmitter receptors, OXPHOS, cadherins, integrins, and gap junction mRNAs. Higher glycemia and insulin resistance were associated, in muscle, with decreased insulin signaling, glycolytic, Krebs' cycle, OXPHOS, and endo/exocytosis mRNAs; in hepatocytes, with reduced insulin signaling, branched chain amino acid catabolism and OXPHOS mRNAs; in adipose tissue, with increased innate immunity and lipid catabolism mRNAs. These data provide a resource for further studies of interorgan communication in glucose homeostasis.
为了确定在胰腺β细胞、肌肉、肝脏和脂肪中协同调节以控制空腹血糖的信号通路，我们给C57Bl/6、DBA/2和Balb/c小鼠喂食常规饲料或高脂饮食5天、13天和33天。我们采用数据融合方法，利用生理学、转录组学和脂质组学数据，来确定在所有研究条件下与空腹血糖相关的器官特异性信号通路。在胰岛中，尽管血糖水平较高，但持续的胰岛素血症与激素和神经递质受体、氧化磷酸化、钙黏蛋白、整合素和间隙连接mRNA的表达降低有关。在肌肉中，较高的血糖和胰岛素抵抗与胰岛素信号传导、糖酵解、三羧酸循环、氧化磷酸化以及胞吐/胞吞作用mRNA的减少有关；在肝细胞中，与胰岛素信号传导、支链氨基酸分解代谢和氧化磷酸化mRNA的减少有关；在脂肪组织中，与先天免疫和脂质分解代谢mRNA的增加有关。这些数据为进一步研究葡萄糖稳态中的器官间通讯提供了资源。
