| First Author | Chau GC | Year | 2017 |
| Journal | J Cell Biol | Volume | 216 |
| Issue | 7 | Pages | 2091-2105 |
| PubMed ID | 28606928 | Mgi Jnum | J:247199 |
| Mgi Id | MGI:5925047 | Doi | 10.1083/jcb.201701085 |
| Citation | Chau GC, et al. (2017) mTOR controls ChREBP transcriptional activity and pancreatic beta cell survival under diabetic stress. J Cell Biol 216(7):2091-2105 |
| abstractText | Impaired nutrient sensing and dysregulated glucose homeostasis are common in diabetes. However, how nutrient-sensitive signaling components control glucose homeostasis and beta cell survival under diabetic stress is not well understood. Here, we show that mice lacking the core nutrient-sensitive signaling component mammalian target of rapamycin (mTOR) in beta cells exhibit reduced beta cell mass and smaller islets. mTOR deficiency leads to a severe reduction in beta cell survival and increased mitochondrial oxidative stress in chemical-induced diabetes. Mechanistically, we find that mTOR associates with the carbohydrate-response element-binding protein (ChREBP)-Max-like protein complex and inhibits its transcriptional activity, leading to decreased expression of thioredoxin-interacting protein (TXNIP), a potent inducer of beta cell death and oxidative stress. Consistent with this, the levels of TXNIP and ChREBP were highly elevated in human diabetic islets and mTOR-deficient mouse islets. Thus, our results suggest that a nutrient-sensitive mTOR-regulated transcriptional network could be a novel target to improve beta cell survival and glucose homeostasis in diabetes. |
