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小鼠空肠中吸收葡萄糖的代谢:花生四烯酸、非甾体抗炎药和类二十烷酸的影响。

Metabolism of absorbed glucose in mouse jejunum: influence of arachidonic acid, non-steroidal anti-inflammatory drugs and eicosanoids.

作者信息

Dempster J A, Kellett G L

机构信息

Department of Biology, University of York, Heslington, UK.

出版信息

Eicosanoids. 1992;5(3-4):177-84.

PMID:1292527
Abstract

The involvement of arachidonic acid and eicosanoids in glucose absorption and metabolism was investigated in isolated mouse jejunum. Characteristics of glucose absorption and its metabolic fate are reported. Reduction in the dietary precursor of arachidonic acid, linoleic acid, and inhibition of phospholipid hydrolysis with mepacrine reduced glucose absorption with no effect on metabolism, although mepacrine increased the proportion of luminal to serosal lactate release. Bradykinin and n-FMLP enhanced metabolism by 2.1- and 2.4-fold, respectively, both reducing the percentage of metabolised glucose converted to lactate, while neither influenced absorption. Both indomethacin and NDGA decreased absorption and enhanced metabolism. The percentage of metabolised glucose converted to lactate decreased and the ratio of luminal to serosal lactate release was unchanged. In the absence of inhibitors, PGE2 (5 microM) decreased absorption by 28%, metabolism by 24% and total lactate production by 32% and LTB4 (20 nM) increased only absorption by 32%. PGE2 release into the perfusates was predominantly serosal (1-10 nM) and was inhibited by indomethacin. PGE2 could not reverse the indomethacin-induced decrease in absorption, but reversed the enhancement of metabolism by 89% and total lactate production by 60%. In conclusion, while the specificity of the drug-related absorptive effects remain unclear, alterations in the utilisation of the absorbed glucose via drug-induced changes in arachidonic acid synthesis and metabolism are apparent. Furthermore, exogenous PGE2 may protect against the effects of indomethacin and itself reduces active glucose absorption, the metabolism of the absorbed glucose and the amount of lactate formed.

摘要

在分离的小鼠空肠中研究了花生四烯酸和类二十烷酸在葡萄糖吸收和代谢中的作用。报告了葡萄糖吸收的特征及其代谢命运。花生四烯酸的膳食前体亚油酸减少,以及用米帕林抑制磷脂水解,均降低了葡萄糖吸收,对代谢无影响,尽管米帕林增加了肠腔向浆膜乳酸释放的比例。缓激肽和N-甲酰甲硫氨酸-亮氨酸-苯丙氨酸分别使代谢增强2.1倍和2.4倍,两者均降低了代谢的葡萄糖转化为乳酸的百分比,而对吸收均无影响。吲哚美辛和去甲二氢愈创木酸均降低吸收并增强代谢。代谢的葡萄糖转化为乳酸的百分比降低,肠腔向浆膜乳酸释放的比例不变。在没有抑制剂的情况下,前列腺素E2(5微摩尔)使吸收降低28%,代谢降低24%,总乳酸生成降低32%,而白三烯B4(20纳摩尔)仅使吸收增加32%。前列腺素E2释放到灌流液中主要是从浆膜侧(1 - 10纳摩尔),并被吲哚美辛抑制。前列腺素E2不能逆转吲哚美辛引起的吸收降低,但能使代谢增强逆转89%,总乳酸生成逆转60%。总之,虽然药物相关吸收作用的特异性尚不清楚,但通过药物诱导的花生四烯酸合成和代谢变化对吸收葡萄糖利用的改变是明显的。此外,外源性前列腺素E2可能预防吲哚美辛的作用,其本身可降低活性葡萄糖吸收、吸收葡萄糖的代谢以及形成的乳酸量。

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