| First Author | Kong L | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 2526 |
| PubMed ID | 38514666 | Mgi Jnum | J:360946 |
| Mgi Id | MGI:7615564 | Doi | 10.1038/s41467-024-46829-0 |
| Citation | Kong L, et al. (2024) Trimethylamine N-oxide impairs beta-cell function and glucose tolerance. Nat Commun 15(1):2526 |
| abstractText | beta-Cell dysfunction and beta-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, beta-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 beta-cell function in vitro and in vivo. Additionally, long-term TMAO exposure promotes beta-cell ER stress, dedifferentiation, and apoptosis and inhibits beta-cell transcriptional identity. Inhibition of TMAO production improves beta-cell GSIS, beta-cell proportion, and glucose tolerance in both male db/db and choline diet-fed mice. These observations identify a role for TMAO in beta-cell dysfunction and maintenance, and inhibition of TMAO could be an approach for the treatment of T2D. |
