Enhanced glucose 6-phosphatase activity in liver of rats exposed to Mg2+-deficient diet

Total hepatic Mg2+ content decreases by >25% in animals maintained for 2 weeks on Mg2+ deficient diet, and results in a >25% increase in glucose 6-phosphatase (G6Pase) activity in isolated liver microsomes in the absence of significant changed in enzyme expression. Incubation of Mg2+-deficient microsomes in the presence of 1 mM external Mg2+ returned G6Pase activity to levels measured in microsomes from animals on normal Mg2+ diet. EDTA addition dynamically reversed the Mg2+ effect. The effect of Mg2+ or EDTA persisted in taurocholic acid permeabilized microsomes. An increase in G6Pase activity was also observed in liver microsomes from rats starved overnight, which presented a ∼15% decrease in hepatic Mg2+ content. In this model, G6Pase activity increased to a lesser extent than in Mg2+-deficient microsomes, but it could still be dynamically modulated by addition of Mg2+ or EDTA. Our results indicate that (1) hepatic Mg2+ content rapidly decreases following starvation or exposure to deficient diet, and (2) the loss of Mg2+ stimulates G6P transport and hydrolysis as a possible compensatory mechanism to enhance intrahepatic glucose availability. The Mg2+ effect appears to take place at the level of the substrate binding site of the G6Pase enzymatic complex or the surrounding phospholipid environment.