| First Author | Nordmann TM | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 6285 |
| PubMed ID | 28740254 | Mgi Jnum | J:253047 |
| Mgi Id | MGI:5926704 | Doi | 10.1038/s41598-017-06731-w |
| Citation | Nordmann TM, et al. (2017) The Role of Inflammation in beta-cell Dedifferentiation. Sci Rep 7(1):6285 |
| abstractText | Chronic inflammation impairs insulin secretion and sensitivity. beta-cell dedifferentiation has recently been proposed as a mechanism underlying beta-cell failure in T2D. Yet the effect of inflammation on beta-cell identity in T2D has not been studied. Therefore, we investigated whether pro-inflammatory cytokines induce beta-cell dedifferentiation and whether anti-inflammatory treatments improve insulin secretion via beta-cell redifferentiation. We observed that IL-1beta, IL-6 and TNFalpha promote beta-cell dedifferentiation in cultured human and mouse islets, with IL-1beta being the most potent one of them. In particular, beta-cell identity maintaining transcription factor Foxo1 was downregulated upon IL-1beta exposure. In vivo, anti-IL-1beta, anti-TNFalpha or NF-kB inhibiting sodium salicylate treatment improved insulin secretion of isolated islets. However, only TNFalpha antagonism partially prevented the loss of beta-cell identity gene expression. Finally, the combination of IL-1beta and TNFalpha antagonism improved insulin secretion of ex vivo isolated islets in a synergistic manner. Thus, while inflammation triggered beta-cell dedifferentiation and dysfunction in vitro, this mechanism seems to be only partly responsible for the observed in vivo improvements in insulin secretion. |
