Lijuan Kong, Qijin Zhao, Xiaojing Jiang, Jinping Hu, Qian Jiang, Li Sheng, Xiaohong Peng, Shusen Wang, Yibing Chen, Yanjun Wan, Shaocong Hou, Xingfeng Liu, Chunxiao Ma, Yan Li, Li Quan, Liangyi Chen, Bing Cui, Pingping Li
β-Cell dysfunction and β-cell loss are hallmarks of type 2 diabetes (T2D). Here, we found that trimethylamine N-oxide (TMAO) at a similar concentration to that found in diabetes could directly decrease glucose-stimulated insulin secretion (GSIS) in MIN6 cells and primary islets from mice or humans. Elevation of TMAO levels impairs GSIS, β-cell proportion, and glucose tolerance in male C57BL/6 J mice. TMAO inhibits calcium transients through NLRP3 inflammasome-related cytokines and induced Serca2 loss, and a Serca2 agonist reversed the effect of TMAO on β-cell function in vitro and in vivo...
March 21, 2024: Nature Communications