Chunk #24 — RESULTS — Txnip deletion protects against ER stress-induced β-cell programmed cell death and diabetes

Source

IRE1α induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress.

Embedded

yes

Text

We then crossed the Txnip−/− and Ins2WT/C96Y mice and followed β-cell apoptosis and development of diabetes in the various cohorts. While the different cohorts have no significant differences in body weight over time (Figure 5D), Txnip−/−; Ins2WT/C96Y mice are strikingly protected from hyperglycemia compared to Txnip+/+; Ins2WT/C96Y mice, for up to 12 weeks (Figure 5E). Moreover, Txnip−/−; Ins2WT/C96Y islets display significantly lower levels of β-cell apoptosis compared to islets from Txnip+/+; Ins2WT/C96Y mice (Figure 5F–G), confirming that TXNIP plays a critical role in promoting programmed β-cell death in this spontaneous ER stress model of diabetes.