| First Author | Lee JH | Year | 2013 |
| Journal | Biochem Biophys Res Commun | Volume | 430 |
| Issue | 3 | Pages | 1109-13 |
| PubMed ID | 23261432 | Mgi Jnum | J:193848 |
| Mgi Id | MGI:5469778 | Doi | 10.1016/j.bbrc.2012.12.029 |
| Citation | Lee JH, et al. (2013) Heat shock protein 90 (HSP90) inhibitors activate the heat shock factor 1 (HSF1) stress response pathway and improve glucose regulation in diabetic mice. Biochem Biophys Res Commun 430(3):1109-13 |
| abstractText | The cytoprotective stress response factor HSF1 regulates the transcription of the chaperone HSP70, which exhibits anti-inflammatory effects and improves insulin sensitivity. We tested the therapeutic potential of this pathway in rodent models of diabetes using pharmacological tools. Activation of the HSF1 pathway was achieved using potent inhibitors of the upstream regulatory protein, HSP90. Treatment with AUY922, a selective HSP90 inhibitor led to robust inhibition of JNK1 phosphorylation, cytoprotection and improved insulin signaling in cells, consistent with effects observed with HSP70 treatment. Chronic dosing with HSP90 inhibitors reversed hyperglycemia in the diabetic db/db mouse model, and improved insulin sensitivity in the diet-induced obese mouse model of insulin resistance, further supporting the concept that the HSF1 pathway is a potentially viable anti-diabetes target. |
