| First Author | Shirakawa J | Year | 2022 |
| Journal | Cell Rep | Volume | 41 |
| Issue | 1 | Pages | 111436 |
| PubMed ID | 36198264 | Mgi Jnum | J:329913 |
| Mgi Id | MGI:7355907 | Doi | 10.1016/j.celrep.2022.111436 |
| Citation | Shirakawa J, et al. (2022) E2F1 transcription factor mediates a link between fat and islets to promote beta cell proliferation in response to acute insulin resistance. Cell Rep 41(1):111436 |
| abstractText | Prevention or amelioration of declining beta cell mass is a potential strategy to cure diabetes. Here, we report the pathways utilized by beta cells to robustly replicate in response to acute insulin resistance induced by S961, a pharmacological insulin receptor antagonist. Interestingly, pathways that include CENP-A and the transcription factor E2F1 that are independent of insulin signaling and its substrates appeared to mediate S961-induced beta cell multiplication. Consistently, pharmacological inhibition of E2F1 blocks beta-cell proliferation in S961-injected mice. Serum from S961-treated mice recapitulates replication of beta cells in mouse and human islets in an E2F1-dependent manner. Co-culture of islets with adipocytes isolated from S961-treated mice enables beta cells to duplicate, while E2F1 inhibition limits their growth even in the presence of adipocytes. These data suggest insulin resistance-induced proliferative signals from adipocytes activate E2F1, a potential therapeutic target, to promote beta cell compensation. |
