| First Author | Hou X | Year | 2023 |
| Journal | Cell Death Dis | Volume | 14 |
| Issue | 10 | Pages | 709 |
| PubMed ID | 37903776 | Mgi Jnum | J:342233 |
| Mgi Id | MGI:7545918 | Doi | 10.1038/s41419-023-06235-8 |
| Citation | Hou X, et al. (2023) Talin-1 inhibits Smurf1-mediated Stat3 degradation to modulate beta-cell proliferation and mass in mice. Cell Death Dis 14(10):709 |
| abstractText | Insufficient pancreatic beta-cell mass and reduced insulin expression are key events in the pathogenesis of diabetes mellitus (DM). Here we demonstrate the high expression of Talin-1 in beta-cells and that deficiency of Talin-1 reduces beta-cell proliferation, which leads to reduced beta-cell mass and insulin expression, thus causing glucose intolerance without affecting peripheral insulin sensitivity in mice. High-fat diet fed exerbates these phenotypes. Mechanistically, Talin-1 interacts with the E3 ligase smad ubiquitination regulatory factor 1 (Smurf1), which prohibits ubiquitination of the signal transducer and activator of transcription 3 (Stat3) mediated by Smurf1, and ablation of Talin-1 enhances Smurf1-mediated ubiquitination of Stat3, leading to decreased beta-cell proliferation and mass. Furthermore, haploinsufficiency of Talin-1 and Stat3 genes, but not that of either gene, in beta-cell in mice significantly impairs glucose tolerance and insulin expression, indicating that both factors indeed function in the same genetic pathway. Finally, inducible deletion Talin-1 in beta-cell causes glucose intolerance in adult mice. Collectively, our findings reveal that Talin-1 functions as a crucial regulator of beta-cell mass, and highlight its potential as a therapeutic target for DM patients. |
