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间氯苯腙羰基氰化物对肾上腺素刺激的离体灌流脂肪细胞脂解作用的可逆性抑制

The reversible inhibition by carbonyl cyanide m-chlorophenyl hydrazone of epinephrine-stimulated lipolysis in perifused isolated fat cells.

作者信息

Huber C T, Duckworth W C, Solomon S S

出版信息

Biochim Biophys Acta. 1981 Dec 23;666(3):462-7. doi: 10.1016/0005-2760(81)90307-6.

DOI:10.1016/0005-2760(81)90307-6
PMID:7326256
Abstract

Lipolysis stimulated in perifused isolated fat cells by 0.5 micrometers epinephrine is an ATP-dependent process which can be monitored by measuring the release of glycerol. The stimulated lipolysis is inhibited to 10 micrometers carbonyl cyanide m-chlorophenyl hydrazone (CCCP), an uncoupler of oxidative phosphorylation. If 20-micrometers glucose is continuously present in the perifusion medium during and after treatment with epinephrine and CCCP, the inhibition of the stimulated lipolysis is reversible when the CCCP is discontinued; otherwise it is not readily reversible. Since 20 micrometers 2-deoxyglucose will not substitute for glucose, metabolism of glucose beyond phosphorylation by hexokinase is concluded to be necessary in order to maintain the reversibility of the inhibition of CCCP. Substitution of 10 micrometers succinate for glucose also did not preserve the reversibility of the CCCP inhibition, and there was no significant difference in the amount of decrease of ATP in fat cells incubated with CCCP and epinephrine in the presence of glucose as compared to the decrease observed in the presence of succinate. The mechanism by which glucose maintains reversibility of the inhibition of stimulated lipolysis by CCCP is therefore not clear.

摘要

0.5微摩尔肾上腺素刺激灌流分离脂肪细胞中的脂解作用是一个依赖ATP的过程,可通过测量甘油释放量来监测。受刺激的脂解作用会被10微摩尔羰基氰化物间氯苯腙(CCCP)抑制,CCCP是氧化磷酸化的解偶联剂。如果在肾上腺素和CCCP处理期间及之后,灌流培养基中持续存在20微摩尔葡萄糖,当停止使用CCCP时,受刺激脂解作用的抑制是可逆的;否则,它不容易逆转。由于20微摩尔2-脱氧葡萄糖不能替代葡萄糖,因此得出结论,葡萄糖在己糖激酶磷酸化之后的代谢对于维持CCCP抑制的可逆性是必要的。用10微摩尔琥珀酸盐替代葡萄糖也不能保持CCCP抑制的可逆性,并且与在琥珀酸盐存在下观察到的ATP减少量相比,在葡萄糖存在下用CCCP和肾上腺素孵育的脂肪细胞中ATP减少量没有显著差异。因此,葡萄糖维持CCCP对刺激脂解作用抑制的可逆性的机制尚不清楚。

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