Akimoto L S, Pedrinho S R, Lopes G, Bazotte R B
Department of Clinical Analysis, State University of Maringá, PR, Brazil.
Res Commun Mol Pathol Pharmacol. 2000;107(1-2):65-77.
The maximal capacity of the liver to produce glucose was examined using a technique, which permited to investigate gluconeogenesis in diabetic fed rats. Diabetes was obtained with an iv injection of alloxan (40 mg/kg). Livers from diabetic fed rats were perfused in situ and gluconeogenesis from different glucose precursors were measured one week after alloxan injection. Hepatic gluconeogenesis from L-alanine (5 mM) was absent. However, increased urea, pyruvate and L-lactate production was observed during L-alanine infusion. Differently of L-alanine, alloxan-diabetic fed rats showed increased hepatic glucose production from pyruvate (5 mM), L-lactate (2 mM) and D-frutose (5 mM). Additionally, increased L-lactate production from pyruvate and pyruvate production from L-lactate were observed. However, pyruvate production from L-lactate was lower in the diabetic group when compared with control group. Moreover similar tendency were observed for L-alanine and D-frutose. Taken together our results demonstrate influence of the cytosolic redox potential (NADH/NAD+ ratio) in the metabolic fate L-alanine. Additionally, in contrast to L-alanine, diabetic rats not only showed increased rate of glucose production from L-glutamine (5 mM) but also higher values than control rats.
采用一种技术检测肝脏产生葡萄糖的最大能力，该技术可用于研究糖尿病喂食大鼠的糖异生作用。通过静脉注射四氧嘧啶（40mg/kg）诱导糖尿病。在四氧嘧啶注射一周后，对糖尿病喂食大鼠的肝脏进行原位灌注，并测量不同葡萄糖前体的糖异生作用。肝脏从L-丙氨酸（5mM）进行糖异生作用缺失。然而，在输注L-丙氨酸期间观察到尿素、丙酮酸和L-乳酸生成增加。与L-丙氨酸不同，四氧嘧啶糖尿病喂食大鼠显示丙酮酸（5mM）、L-乳酸（2mM）和D-果糖（5mM）的肝脏葡萄糖生成增加。此外，观察到丙酮酸生成L-乳酸以及L-乳酸生成丙酮酸均增加。然而，与对照组相比，糖尿病组中L-乳酸生成丙酮酸的量较低。此外，L-丙氨酸和D-果糖也观察到类似趋势。综合来看，我们的结果表明胞质氧化还原电位（NADH/NAD+比值）对L-丙氨酸代谢命运有影响。此外，与L-丙氨酸不同，糖尿病大鼠不仅显示L-谷氨酰胺（5mM）的葡萄糖生成速率增加，而且其值高于对照大鼠。
