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体内输注胰高血糖素样肽-2诱导大鼠空肠中钠-葡萄糖协同转运蛋白1转运活性上调。

Upregulation of SGLT-1 transport activity in rat jejunum induced by GLP-2 infusion in vivo.

作者信息

Cheeseman C I

机构信息

Department of Physiology, University of Alberta, Edmonton, Canada.

出版信息

Am J Physiol. 1997 Dec;273(6):R1965-71. doi: 10.1152/ajpregu.1997.273.6.R1965.

Abstract

The effect of in vivo infusion of the peptide hormone glucagon-like peptide 2 (GLP-2) on glucose transport across the rat jejunal brush-border membrane (BBM) was assessed using isolated membrane vesicles. A 2-h infusion of GLP-2 produced a marked acceleration of sodium-dependent glucose uptake into BBM vesicles with a significant overshoot. There was no change in vesicle space or permeability resulting from the hormone infusion. Kinetic analysis showed this stimulation to be the result of a three-fold increase in the maximal rate of transport, with no consistent change in the affinity constant (Km). The time course of this response showed that the effect was observable, but smaller, after only 30 min of hormone infusion and was maximal after 1 h. Sodium-dependent phloridzin binding to the membrane vesicles showed a parallel increase in maximal binding after 1 and 2 h of hormone infusion. Western blotting showed a similar increase in sodium-dependent glucose transporter 1 (SGLT-1) abundance. The effect of GLP-2 could be blocked by luminal brefeldin A or wortmannin. These results indicate that GLP-2 is able to induce trafficking of SGLT-1 from an intracellular pool into the BBM within 60 min and that phosphoinositol 3-kinase may well be involved in the intracellular signaling pathway in this response.

摘要

利用分离的膜囊泡评估了体内注入肽类激素胰高血糖素样肽2(GLP - 2)对大鼠空肠刷状缘膜(BBM)葡萄糖转运的影响。注入GLP - 2 2小时显著加速了BBM囊泡中钠依赖型葡萄糖摄取,并出现明显的超调现象。激素注入并未导致囊泡空间或通透性发生变化。动力学分析表明,这种刺激是转运最大速率增加三倍的结果,亲和常数(Km)无一致变化。该反应的时间进程表明,仅注入激素30分钟后效应即可观察到,但较小,1小时后达到最大。激素注入1小时和2小时后,钠依赖型根皮苷与膜囊泡的结合显示最大结合量平行增加。蛋白质免疫印迹显示钠依赖型葡萄糖转运体1(SGLT - 1)丰度有类似增加。GLP - 2的作用可被腔内布雷菲德菌素A或渥曼青霉素阻断。这些结果表明,GLP - 2能够在60分钟内诱导SGLT - 1从细胞内池转运至BBM,并且磷脂酰肌醇3激酶很可能参与了这一反应的细胞内信号通路。

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