葡萄糖对四氧嘧啶诱导的β细胞损伤的保护机制：ATP的关键作用。

Protective mechanism of glucose against alloxan-induced beta-cell damage: pivotal role of ATP.

作者信息

Rho H W, Lee J N, Kim H R, Park B H, Park J W

机构信息

Department of Biochemistry, School of Medicine and Institute for Medical Science, Chonbuk National University, Chonju, Korea.

出版信息

Exp Mol Med. 2000 Mar 31;32(1):12-7. doi: 10.1038/emm.2000.3.

DOI:10.1038/emm.2000.3

PMID:10762056

Abstract

Glucose prevents the development of diabetes induced by alloxan. In the present study, the protective mechanism of glucose against alloxan-induced beta-cell damage was investigated using HIT-T 15 cell, a Syrian hamster transformed beta-cell line. Alloxan caused beta-cell damages with DNA fragmentation, inhibition of glucose-stimulated insulin release, and decrease of cellular ATP level, but all of these beta-cell damages by alloxan were prevented by the presence of 20 mM glucose. Oligomycin, a specific inhibitor of ATP synthase, completely abolished the protective effects of glucose against alloxan-induced cell damage. Furthermore, treatment of nuclei isolated from HIT-T15 cells with ATP significantly prevented the DNA fragmentation induced by Ca2+. The results indicate that ATP produced during glucose metabolism plays a pivotal role in the protection of glucose against alloxan-induced beta-cell damage.

摘要

葡萄糖可预防四氧嘧啶诱导的糖尿病。在本研究中，使用叙利亚仓鼠转化的β细胞系HIT-T 15细胞，研究了葡萄糖对四氧嘧啶诱导的β细胞损伤的保护机制。四氧嘧啶导致β细胞损伤，出现DNA片段化、葡萄糖刺激的胰岛素释放受抑制以及细胞ATP水平降低，但20 mM葡萄糖的存在可预防四氧嘧啶所致的所有这些β细胞损伤。寡霉素是ATP合酶的特异性抑制剂，它完全消除了葡萄糖对四氧嘧啶诱导的细胞损伤的保护作用。此外，用ATP处理从HIT-T15细胞分离的细胞核，可显著预防Ca2+诱导的DNA片段化。结果表明，葡萄糖代谢过程中产生的ATP在葡萄糖对四氧嘧啶诱导的β细胞损伤的保护中起关键作用。