TI - The Promoter of TXNIP Contains Conserved Regulatory Elements That May Account for Its Reciprocal Regulation by Insulin and Glucose . AB - We hypothesized that the reciprocal regulation of TXNIP expression by insulin and glucose is likely mediated by highly conserved regulatory elements in the vicinity of its promoter (Figure S2) . First , it contains tandem E-boxes that have been shown to account for the brisk response of TXNIP to glucose in the pancreas [40] . The promoter also contains an evolutionarily conserved binding site for the forkhead family of transcription factors . Because these forkhead family members are known to be excluded from the nucleus via Akt -mediated PHOSphorylation downstream of insulin signaling [41] , and since TXNIP induction by glucose is blunted by the activation of the phosphatidylinositol-3-kinase/Akt pathway [38] , this class of transcription factors represent excellent candidate mediators of the insulin-stimulated repression of TXNIP .