Peled-Kamar M, Degani H, Bendel P, Margalit R, Groner Y
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.
Brain Res. 1998 Nov 9;810(1-2):138-45. doi: 10.1016/s0006-8993(98)00899-3.
The gene for the liver-type subunit of phosphofructokinase (PFKL) resides on chromosome 21 and is overexpressed in Down syndrome (DS) patients. Transgenic PFKL (Tg-PFKL) mice with elevated levels of PFKL were used to determine whether, as in DS, overexpression of PFKL was also associated with altered sugar metabolism. We found that Tg-PFKL mice had an abnormal glucose metabolism with reduced clearance rate from blood and enhanced metabolic rate in brain. Transgenic-PFKL mice exhibited elevated activity of phosphofructokinase in both blood and brain, as compared to control non-transgenic (ntg) mice. Following glucose infusion, the rate of glucose clearance from the blood of Tg-PFKL mice was significantly slower than that of control ntg mice, although the basal blood glucose levels were similar. However, unlike the slower rate of glucose metabolism in blood, the initial rate of glucose utilization in the brain of the transgenic mice, was 58% faster than in control ntg mice. This was determined by infusion of [1-13C]-glucose followed by in vivo nuclear magnetic resonance (NMR) measurements of brain glucose metabolism. The faster utilization of glucose in Tg-PFKL brain is similar to the increased rate of cerebral glucose metabolism found in the brain of young adult DS patients, which may play a role in the etiology of their cognitive disabilities.
磷酸果糖激酶（PFKL）肝脏型亚基的基因位于21号染色体上，在唐氏综合征（DS）患者中过度表达。利用PFKL水平升高的转基因PFKL（Tg-PFKL）小鼠来确定，与DS患者一样，PFKL的过度表达是否也与糖代谢改变有关。我们发现，Tg-PFKL小鼠存在异常的葡萄糖代谢，血液清除率降低，大脑代谢率提高。与对照非转基因（ntg）小鼠相比，转基因PFKL小鼠的血液和大脑中磷酸果糖激酶活性均升高。葡萄糖输注后，尽管基础血糖水平相似，但Tg-PFKL小鼠血液中的葡萄糖清除率明显慢于对照ntg小鼠。然而，与血液中较慢的葡萄糖代谢速率不同，转基因小鼠大脑中葡萄糖的初始利用速率比对照ntg小鼠快58%。这是通过输注[1-13C]-葡萄糖，然后对大脑葡萄糖代谢进行体内核磁共振（NMR）测量来确定的。Tg-PFKL大脑中葡萄糖的更快利用类似于在年轻成年DS患者大脑中发现的大脑葡萄糖代谢增加，这可能在其认知障碍的病因中起作用。
