Glucose 6-phosphate hydrolysis is activated by glucagon in a low temperature-sensitive manner

被引:17
作者
Ichai, C
Guignot, L
El-Mir, MY
Nogueira, V
Guigas, B
Chauvin, C
Fontaine, E
Mithieux, G
Leverve, XM
机构
[1] Univ Grenoble 1, Lab Bioenerget Fondamentale & Appl, F-38041 Grenoble, France
[2] Fac Med Laennec, INSERM, U449, F-69372 Lyon, France
关键词
D O I
10.1074/jbc.M010186200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Glucagon affects liver glucose metabolism mainly by activating glycogen breakdown and by inhibiting pyruvate kinase, whereas a possible effect on glucose-6-phosphatase has also been suggested. Although such a target is of physiological importance for liver glucose production it was never proven. By using a model of liver cells, perifused. with dihydroxyacetone, we show here that the acute stimulation of gluconeogenesis by glucagon (10(-7) M) was not related to the significant inhibition of pyruvate kinase but to a dramatic activation of the hydrolysis of glucose 6-phosphate. We failed to find an acute change in glucose-6-phosphatase activity by glucagon, but the increase in glucose 6-phosphate hydrolysis was abolished at 21 degreesC; conversely the effect on pyruvate kinase was not affected by temperature. The activation of glucose 6-phosphate hydrolysis by glucagon was confirmed in vivo, in postabsorptive rats receiving a constant infusion of glucagon, by the combination of a 2-fold increase in hepatic glucose production and a 60% decrease in liver glucose 6-phosphate concentration. Besides the description of a novel effect of glucagon on glucose 6-phosphate hydrolysis by a temperature-sensitive mechanism, this finding could represent an important breakthrough in the understanding of type II diabetes, because glucose 6-phosphate is proposed to be a key molecule in the transcriptional effect of glucose.
引用
收藏
页码:28126 / 28133
页数:8
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