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Glucose 6-Phosphate Hydrolysis Is Activated by Glucagon in a Low Temperature-sensitive Manner

2001; Elsevier BV; Volume: 276; Issue: 30 Linguagem: Inglês

10.1074/jbc.m010186200

1083-351X

Carole Ichaï, Ludovic Guignot, Mohamad Y. El-Mir, Véronique Nogueira, Bruno Guigas, Christiane Chauvin, Éric Fontaine, Gilles Mithieux, Xavier Leverve,

Glycogen Storage Diseases and Myoclonus

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 °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.