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荷瘤大鼠肝脏中葡萄糖转运蛋白2免疫表达的改变

Alteration in immunoexpression of glucose transporter 2 in liver of tumour-bearing rats.

作者信息

Doi C, Noguchi Y, Ito T, Yoshikawa T, Makino T, Matsumoto A

机构信息

First Department of Surgery, Yokohama City University School of Medicine, Japan.

出版信息

Int J Exp Pathol. 1998 Feb;79(1):25-31. doi: 10.1046/j.1365-2613.1998.00035.x.

Abstract

To elucidate interactions between the glucose transport system and hepatic glucose production in the tumour-bearing state, glycogen storage, expression of glucose transporter isoform 2 (Glut 2) and activities of glucose-6-phosphatase (G-6-Pase) and hexokinase were histochemically examined in hepatocytes of tumour-bearing rats. Five male F344 rats, subcutaneously inoculated with methylcholanthrene (MCA)-induced sarcoma cells were compared with five pair-fed animals and four ad libitum fed controls. Glycogen storage was markedly decreased in liver cells of tumour-bearing rats compared to in those of control animals. Glut 2 immunoreactivity was uniformly seen in the cellular membrane of hepatocytes from control animals. In rats bearing sarcoma, the staining intensity was significantly decreased, suggesting that Glut 2 with its bi-directional transport capacity was down-regulated in the tumour-bearing state. Positive staining for hexokinase activity was located in the perivenous area in livers from control animals and was more diffusely located and more intense in livers from tumour-bearing animals. G-6-Pase activity, limited to the peripheral area in livers from controls, extended to the intermediate area and had stronger reactivity in livers from tumour-bearing animals. In the tumour-bearing cachectic condition, glucose may be partially consumed by a futile cycle, hepatic metabolic zonation was disturbed, and the release of glucose from the liver may not be mediated by a facilitative glucose transporter-2.

摘要

为阐明荷瘤状态下葡萄糖转运系统与肝脏葡萄糖生成之间的相互作用,对荷瘤大鼠肝细胞中的糖原储存、葡萄糖转运蛋白2(Glut 2)的表达以及葡萄糖-6-磷酸酶(G-6-Pase)和己糖激酶的活性进行了组织化学检测。将5只皮下接种甲基胆蒽(MCA)诱导的肉瘤细胞的雄性F344大鼠与5只配对喂养的动物及4只自由进食的对照动物进行比较。与对照动物相比,荷瘤大鼠肝细胞中的糖原储存明显减少。在对照动物肝细胞的细胞膜上均可见Glut 2免疫反应性。在肉瘤大鼠中,染色强度显著降低,这表明具有双向转运能力的Glut 2在荷瘤状态下表达下调。对照动物肝脏中己糖激酶活性的阳性染色位于肝静脉周围区域,而在荷瘤动物肝脏中分布更弥散且强度更高。G-6-Pase活性在对照动物肝脏中局限于周边区域,在荷瘤动物肝脏中扩展至中间区域且反应性更强。在荷瘤恶病质状态下,葡萄糖可能部分通过无效循环被消耗,肝脏代谢分区受到干扰,肝脏中葡萄糖的释放可能不由易化葡萄糖转运蛋白-2介导。

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