Lypova N M, Minchenko D O, Ratushna O O, Bozhko I V, Tsuchihara K, Esumi H, Minchenko O H
Ukr Biokhim Zh (1999). 2010 Jan-Feb;82(1):90-9.
We studied the expression mRNA of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-2 (PFKFB-2) in the rat lung and kidney in experimental diabetes mellitus. For investigation we select two isoforms of PFKFB-2 with different C-terminus. The level of the expression of both PFKFB-2 mRNA isoforms is decreased in the kidney and lung in rats with experimental diabetes mellitus respect to the control animals. Moreover, four new alternative splice variants of PFKFB-2 mRNA were identified in the rat kidney. These splice variants of PFKFB-2 mRNA have different inserts and/or deletions in 6-phosphofructo-2-kinase as well as in fructose-2,6-bisphosphatase part of PFKFB-2. Three alternative splice variants cannot encode active 6-phosphofructo-2-kinase as a result of deletion of two catalytic domains (E and F). They encode fructose-2,6-bisphosphatase. It was shown that these alternative splice variants express in the kidney and lung and that this expression changes in rats with experimental diabetes mellitus with respect to the control animals. The results of this investigation clearly demonstrated that diabetes mellitus significantly affects the expression and alternative splicing of PFKFB-2 in the kidney and lungs and showed the complexity of regulatory mechanisms of glucose metabolism in this disease.
我们研究了实验性糖尿病大鼠肺和肾中6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶-2（PFKFB-2）的mRNA表达。为了进行研究，我们选择了两种具有不同C末端的PFKFB-2同工型。与对照动物相比，实验性糖尿病大鼠肾和肺中两种PFKFB-2 mRNA同工型的表达水平均降低。此外，在大鼠肾中鉴定出四种新的PFKFB-2 mRNA可变剪接变体。这些PFKFB-2 mRNA的剪接变体在6-磷酸果糖-2-激酶以及PFKFB-2的果糖-2,6-二磷酸酶部分具有不同的插入和/或缺失。由于两个催化结构域（E和F）的缺失，三种可变剪接变体无法编码有活性的6-磷酸果糖-2-激酶。它们编码果糖-2,6-二磷酸酶。结果表明，这些可变剪接变体在肾和肺中表达，并且在实验性糖尿病大鼠中相对于对照动物，这种表达发生了变化。本研究结果清楚地表明，糖尿病显著影响肾和肺中PFKFB-2的表达和可变剪接，并显示了该疾病中葡萄糖代谢调节机制的复杂性。
