| First Author | Weng Q | Year | 2020 |
| Journal | Cell Death Differ | Volume | 27 |
| Issue | 1 | Pages | 130-145 |
| PubMed ID | 31097787 | Mgi Jnum | J:303563 |
| Mgi Id | MGI:6510088 | Doi | 10.1038/s41418-019-0344-3 |
| Citation | Weng Q, et al. (2020) STAT3 dictates beta-cell apoptosis by modulating PTEN in streptozocin-induced hyperglycemia. Cell Death Differ 27(1):130-145 |
| abstractText | Insufficient pancreatic beta-cell mass or insulin-producing beta-cells are implicated in all forms of diabetes mellitus. However, the molecular mechanisms underlying beta-cell destruction are complex and not fully defined. Here we observed that activation of STAT3 is intensely and specifically inhibited in beta-cells under hyperglycemic conditions. By knocking out STAT3 specifically in mouse beta-cells, we found that the loss of STAT3 sensitized mice to three low doses of STZ stimulation resulting in hyperglycemia. Mechanistically, accumulating PTEN, induced by STAT3 deficiency, directly represses phosphorylation of AKT, which negatively modulates transcription factor activation, dysregulates beta-cell function, positively promotes apoptotic signaling, and finally induces beta-cell apoptosis. Notably, the defective secretion of insulin and beta-cells apoptosis was completely rescued by PTEN ablation in STAT3-null islets or PTEN inhibitor bpv(phen) treatment. Thus our data suggest that STAT3 is a vital modulator of beta-cell survival and function, highlighting a critical role for STAT3 in the negative regulation of PTEN-AKT signaling pathway associated with beta-cell dysfunction and apoptosis. |
