Andrikopoulos S, Rosella G, Kaczmarczyk S J, Zajac J D, Proietto J
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Victoria, Austria.
Metabolism. 1996 May;45(5):622-6. doi: 10.1016/s0026-0495(96)90034-7.
Increased hepatic glucose production, a feature of (non-insulin-dependent diabetes mellitus [NIDDM]), is present at an early age in the New Zealand Obese (NZO) mouse and is associated with impaired suppression of the gluconeogenic enzyme, fructose-1,6-bisphosphatase (FBPase). The aim of this study was to further characterize the abnormality in the regulation of hepatic FBPase in NZO mice versus New Zealand Chocolate (NZC) control mice. At 20 weeks of age, NZO mice have elevated FBPase activity (65.3 +/- 7.9 v 46.7 +/- 5.0 micromol/min/mg protein, P =.07) and protein levels (31.7 +/- 3.1 v 22.5 +/- 2.8 arbitrary units, P < .05), but not mRNA levels (0.18 +/- 0.03 v 0.16 +/- 0.03 arbitrary units). Elevated FBPase activity and protein levels in NZO mice were also shown at 4 to 6 weeks of age, but not in 1-day-old mice, suggesting that the increase occurs between birth and weaning. The Km of the enzyme was the same in NZO and NZC mice (3.7 +/- 0.5 v 5.0 +/- 0.9 micromol/L, NZO v NZC). The regulation of FBPase by the competitive inhibitor, fructose-2,6-bisphosphate ([Fru(2,6)Pz] 5 micromol/L) measured over a range of substrate concentrations (2.5 to 80 micromol/L) was similar between NZO and control mice (Km in the presence of Fru(2,6)Pz, 10.8 +/- v 1.9 v 13.2 +/- 3.3 micromol/L, NZO v NZC). It is concluded that increased FBPase activity in the NZO mouse is due to elevated protein levels, and that this appears to be due to a failure of the normal decrease that occurs following birth in control animals.
肝脏葡萄糖生成增加是（非胰岛素依赖型糖尿病 [NIDDM]）的一个特征，在新西兰肥胖（NZO）小鼠幼年时就已出现，且与糖异生酶果糖-1,6-二磷酸酶（FBPase）抑制作用受损有关。本研究的目的是进一步阐明NZO小鼠与新西兰巧克力（NZC）对照小鼠相比，肝脏FBPase调节异常的特征。20周龄时，NZO小鼠的FBPase活性（65.3±7.9对46.7±5.0微摩尔/分钟/毫克蛋白质，P = 0.07）和蛋白质水平（31.7±3.1对22.5±2.8任意单位，P < 0.05）升高，但mRNA水平（0.18±0.03对0.16±0.03任意单位）未升高。NZO小鼠在4至6周龄时也表现出FBPase活性和蛋白质水平升高，但1日龄小鼠未出现，这表明这种增加发生在出生至断奶之间。该酶的Km在NZO和NZC小鼠中相同（3.7±0.5对5.0±0.9微摩尔/升，NZO对NZC）。在一系列底物浓度（2.5至80微摩尔/升）范围内，用竞争性抑制剂果糖-2,6-二磷酸（[Fru(2,6)Pz] 5微摩尔/升）对FBPase的调节在NZO小鼠和对照小鼠之间相似（在存在Fru(2,6)Pz时的Km，10.8±1.9对13.2±3.3微摩尔/升，NZO对NZC）。得出的结论是，NZO小鼠中FBPase活性增加是由于蛋白质水平升高，而这似乎是由于对照动物出生后正常下降的过程失败所致。
