| Autor: |
Jun Shirakawa, Yu Togashi, Giorgio Basile, Tomoko Okuyama, Ryota Inoue, Megan Fernandez, Mayu Kyohara, Dario F. De Jesus, Nozomi Goto, Wei Zhang, Takahiro Tsuno, Tatsuya Kin, Hui Pan, Jonathan M. Dreyfuss, A.M. James Shapiro, Peng Yi, Yasuo Terauchi, Rohit N. Kulkarni |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 41, Iss 1, Pp 111436- (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2022.111436 |
| Popis: |
Summary: Prevention or amelioration of declining β cell mass is a potential strategy to cure diabetes. Here, we report the pathways utilized by β 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 β cell multiplication. Consistently, pharmacological inhibition of E2F1 blocks β-cell proliferation in S961-injected mice. Serum from S961-treated mice recapitulates replication of β cells in mouse and human islets in an E2F1-dependent manner. Co-culture of islets with adipocytes isolated from S961-treated mice enables β 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 β cell compensation. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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