| First Author | Blandino-Rosano M | Year | 2023 |
| Journal | Mol Metab | Volume | 75 |
| Pages | 101769 | PubMed ID | 37423392 |
| Mgi Jnum | J:355449 | Mgi Id | MGI:7515780 |
| Doi | 10.1016/j.molmet.2023.101769 | Citation | Blandino-Rosano M, et al. (2023) Raptor levels are critical for beta-cell adaptation to a high-fat diet in male mice. Mol Metab 75:101769 |
| abstractText | OBJECTIVE: The essential role of raptor/mTORC1 signaling in beta-cell survival and insulin processing has been recently demonstrated using raptor knock-out models. Our aim was to evaluate the role of mTORC1 function in adaptation of beta-cells to insulin resistant state. METHOD: Here, we use mice with heterozygous deletion of raptor in beta-cells (betara(Het)) to assess whether reduced mTORC1 function is critical for beta-cell function in normal conditions or during beta-cell adaptation to high-fat diet (HFD). RESULTS: Deletion of a raptor allele in beta-cells showed no differences at the metabolic level, islets morphology, or beta-cell function in mice fed regular chow. Surprisingly, deletion of only one allele of raptor increases apoptosis without altering proliferation rate and is sufficient to impair insulin secretion when fed a HFD. This is accompanied by reduced levels of critical beta-cell genes like Ins1, MafA, Ucn3, Glut2, Glp1r, and specially PDX1 suggesting an improper beta-cell adaptation to HFD. CONCLUSION: This study identifies that raptor levels play a key role in maintaining PDX1 levels and beta-cell function during the adaptation of beta-cell to HFD. Finally, we identified that Raptor levels regulate PDX1 levels and beta-cell function during beta-cell adaptation to HFD by reduction of the mTORC1-mediated negative feedback and activation of the AKT/FOXA2/PDX1 axis. We suggest that Raptor levels are critical to maintaining PDX1 levels and beta-cell function in conditions of insulin resistance in male mice. |
