TXNIP levels are elevated in the muscle of diabetic humans and mice (Parikh et al., 2007), and TXNIP-deficient mice have increased adiposity while remaining insulin-sensitive (Hui et al., 2004). TXNIP is strongly induced in response to glucotoxicity, and promotes apoptosis of β-cells (Chen et al., 2008; Shalev, 2008). A recent study linked glucose toxicity and oxidative stress through TXNIP to downstream activation of the NLRP3 inflammasome and secretion of IL-1β (Zhou et al., 2010). Here we found that the loss of TXNIP prevents β-cell apoptosis and diabetes caused by ER stress in the Akita mouse. Thus through a link to the NLRP3 inflammasome, TXNIP may be well-positioned to mediate both cell autonomous and nonautonomous destructive responses to diverse DAMPs, including unfolded proteins in the ER.
