Other
20 Authors
- Wang Y,
- Darragh LB,
- Qi L,
- Ma M,
- Soleimanpour SA,
- Ji Y,
- Oberholzer J,
- Sun S,
- Kim H,
- Liu C,
- Naji A,
- Gannon M,
- Xing Y,
- Carboneau BA,
- An D,
- Shirakawa J,
- Kersten S,
- He Y,
- Kulkarni RN,
- Shrestha N
| First Author | Ji Y | Year | 2019 |
| Journal | Nat Immunol | Volume | 20 |
| Issue | 6 | Pages | 677-686 |
| PubMed ID | 31110312 | Mgi Jnum | J:282492 |
| Mgi Id | MGI:6381049 | Doi | 10.1038/s41590-019-0396-z |
| Citation | Ji Y, et al. (2019) Toll-like receptors TLR2 and TLR4 block the replication of pancreatic beta cells in diet-induced obesity. Nat Immunol 20(6):677-686 |
| abstractText | Consumption of a high-energy Western diet triggers mild adaptive beta cell proliferation to compensate for peripheral insulin resistance; however, the underlying molecular mechanism remains unclear. In the present study we show that the toll-like receptors TLR2 and TLR4 inhibited the diet-induced replication of beta cells in mice and humans. The combined, but not the individual, loss of TLR2 and TLR4 increased the replication of beta cells, but not that of alpha cells, leading to enlarged beta cell area and hyperinsulinemia in diet-induced obesity. Loss of TLR2 and TLR4 increased the nuclear abundance of the cell cycle regulators cyclin D2 and Cdk4 in a manner dependent on the signaling mediator Erk. These data reveal a regulatory mechanism controlling the proliferation of beta cells in diet-induced obesity and suggest that selective targeting of the TLR2/TLR4 pathways may reverse beta cell failure in patients with diabetes. |
