期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 346, 期 3, 页码 1067-1074出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2006.06.027
关键词
GLP-1; exendin-4; incretin; diabetes; pancreatic islets; VDUP1; oxidative stress
Exenatide (Ex-4) is a novel anti-diabetic drug that stimulates insulin secretion and enhances P-cell mass, but the mechanisms involved are not fully understood. We found that Ex-4 protects INS-1 P-cells against oxidative stress-induced apoptosis (TUNEL) and also reduces expression (mRNA and protein) of thioredoxin-interacting protein (TXNIP), a pro-apoptotic factor involved in beta-cell glucose toxicity and oxidative stress. This reduction was observed in INS-1 cells, mouse, and human islets as well as in wild-type mice receiving Ex-4 and was accompanied by decreased expression of the apoptotic factors caspase-3 and Bax. To determine whether Ex-4-mediated TXNIP reduction is critical for this inhibition of apoptosis, we stably overexpressed TXNIP in INS-1 cells, which completely blunted the anti-apoptotic Ex-4 effects. Thus, Ex-4 inhibits apoptosis by reducing TXNIP expression and early initiation of Ex-4 treatment may help preserve endogenous beta-cell mass, protect against oxidative stress, and delay type 2 diabetes progression. (c) 2006 Elsevier Inc. All rights reserved.
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