Overexpression of thioredoxin‐interacting protein (TXNIP) is associated with reduced insulin sensitivity and β‐cell apoptosis. We have previously shown that W2476 inhibited high glucose‐induced TXNIP expression at both mRNA and protein levels in INS‐1E cells. In this study, we describe structural modification and optimization of W2476 leading to three more active derivatives, 8d, 8g, and 9h, capable of suppressing TXNIP expression in BG73 and INS‐1E cells, increasing insulin production, and reducing high glucose‐induced apoptosis in INS‐1E cells.

中文翻译：

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腺嘌呤衍生物可逆转高葡萄糖诱导的硫氧还蛋白相互作用蛋白的过表达

硫氧还蛋白相互作用蛋白（TXNIP）的过表达与胰岛素敏感性降低和β细胞凋亡有关。先前我们已经证明，W2476在INS-1E细胞的mRNA和蛋白水平上均抑制了葡萄糖诱导的高TXNIP表达。在这项研究中，我们描述了W2476的结构修饰和优化，从而导致了三种更多的活性衍生物8d，8g和9h，它们能够抑制BG73和INS-1E细胞中TXNIP的表达，增加胰岛素的产生并减少高糖诱导的细胞凋亡在INS-1E单元中。