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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.

We show that every doubly periodic planar map is isomorphic to one whose countries are convex, and that the corresponding statement is false in higher dimensions.

Metformin is one of the most widely used antidiabetic drugs in the treatment of type 2 diabetes. On top of its glucose- lowering properties, metformin also lowers plasma very low-density lipoprotein (VLDL) in type 2 diabetes patients by a mechanism that remains to be elucidated. The aim of this study was to investigate the effects and underlying molecular mechanisms of metformin on VLDL metabolism in APOE*3-Leiden.CETP mice, a unique mouse model for human-like lipoprotein metabolism.