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

Abstract : 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 degrees C; 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.
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Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2001, 276 (30), pp.28126-33. 〈10.1074/jbc.M010186200〉
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Carole Ichai, Ludovic Guignot, Mohamad Yehia El-Mir, Véronique Nogueira, Bruno Guigas, et al.. Glucose 6-phosphate hydrolysis is activated by glucagon in a low temperature-sensitive manner.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2001, 276 (30), pp.28126-33. 〈10.1074/jbc.M010186200〉. 〈inserm-00389995〉

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