Adenine derivatives invert high glucose‐induced thioredoxin‐interacting protein overexpression.

Autor:	Zhong, Li, Liu, Qing, Ting, Yan Sie, Thien, Vun Yien, Binti Kalong, Nurwafa Syafiqah, Yang, Dehua, Wang, Ming‐Wei
Předmět:	ADENINE derivatives GLUCOSE PROTEIN overexpression THIOREDOXIN APOPTOSIS
Zdroj:	Chemical Biology & Drug Design; Dec2018, Vol. 92 Issue 6, p1998-2008, 11p
Abstrakt:	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. Overexpression of TXNIP is associated with reduced insulin sensitivity and β‐cell apoptosis. Our previous work disclosed that W2476 could inhibit high glucose‐induced TXNIP overexpression at both mRNA and protein levels in INS‐1E cells. Subsequent work on the structural modification and optimization of W2476 led 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. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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