Toyoda Y, Ito Y, Tanigawa K, Miwa I
Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Arch Histol Cytol. 2000 Jul;63(3):243-8. doi: 10.1679/aohc.63.243.
We examined sugar-induced translocation of glucokinase in cultured hepatocytes from Otsuka Long-Evans Tokushima Fatty and Goto-Kakizaki rats, animal models of type 2 diabetes, and compared this with that in Long-Evans Tokushima Otsuka and Wistar rats, respectively, as control strains. When hepatocytes from the four strains were incubated with 5 mM glucose, glucokinase was present predominantly in the nuclei. Higher concentrations of glucose, 5 mM glucose plus 1 mM fructose, and 5 mM glucose plus 1 mM sorbitol all induced the translocation of glucokinase from the nucleus to the cytoplasm in hepatocytes from these rats. The extent of glucokinase translocation under these conditions, however, was less marked in both diabetic rat types than in the control rats. The extent of the phosphorylation of glucose as estimated by the release of 3H2O from [2- 3H] glucose is significantly lower in Goto-Kakizaki rats than in Wistar rats. The results indicate that the translocation of glucokinase is impaired in the hepatocytes of diabetic rats. They also suggest that the impaired translocation of glucokinase is associated with abnormal hepatic glucose metabolism in type 2 diabetes.
我们检测了葡萄糖诱导的大冢长-艾维德岛肥胖大鼠（Otsuka Long-Evans Tokushima Fatty）和五岛崎大鼠（Goto-Kakizaki）（2型糖尿病动物模型）培养肝细胞中葡萄糖激酶的转位情况，并分别与作为对照品系的大冢长-艾维德岛大鼠（Long-Evans Tokushima Otsuka）和Wistar大鼠进行比较。当用5 mM葡萄糖孵育这四种品系的肝细胞时，葡萄糖激酶主要存在于细胞核中。更高浓度的葡萄糖、5 mM葡萄糖加1 mM果糖以及5 mM葡萄糖加1 mM山梨醇均诱导这些大鼠肝细胞中的葡萄糖激酶从细胞核转位至细胞质。然而，在这些条件下，两种糖尿病大鼠品系中葡萄糖激酶的转位程度均不如对照大鼠明显。通过[2-³H]葡萄糖释放³H₂O估算的葡萄糖磷酸化程度在五岛崎大鼠中显著低于Wistar大鼠。结果表明，糖尿病大鼠肝细胞中葡萄糖激酶的转位受损。它们还提示，葡萄糖激酶转位受损与2型糖尿病中肝脏葡萄糖代谢异常有关。
