Three experiments were carried out to explore the effects of magnesium deficiency on the activities of the hepatic gluconeogenic enzymes. In Experiment I rats were fed, ad libitum, diets adequate (control) or deficient in magnesium for 12 days. One half of the rats from each treatment group were then fasted for 24 hours. The remaining rats were allowed to eat. The rats were subsequently sacrificed and the following parameters were measured: blood glucose and plasma magnesium, liver magnesium and protein, and the activities of liver glucose-6-phosphatase (G6Pase), fructose 1, 6-bisphosphatase (FDPase), and phosphoenolpyruvate carboxykinase (PEPCK). In Experiments II and III rats were meal-fed diets adequate or deficient in magnesium; in addition, a group of rats was pair-fed to the magnesium-deficient group to test for the effects of anorexia. After 17 days the rats were fasted for 20 hours then sacrificed. The parameters measured in Experiment I were again assessed except liver FDPase and G6Pase were not measured in Experiment III.

Feeding a diet deficient in magnesium to the rat produced symptoms characteristic of the deficient state. These symptoms included hyperemia, skin lesions, anorexia, decreased weight gain, and decreased plasma magnesium levels. Anorexia accounted for part, but not all of the decreased weight gain. The concentration of magnesium in the liver of the magnesium-deficient rat was unchanged relative to control values. In the fasted rat, relative to the fed rat, the activities of liver glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) were increased while that of FDPase was decreased. The response to fasting was similar in magnesium deficient and control rats. In the magnesium-deficient rat, relative to the control rat, the activities of G6Pase and FDPase were unchanged, while that of PEPCK was increased. Anorexia was not responsible for the changes in the activity of PEPCK. Since magnesium was not lost from the liver in magnesium deficiency a direct action of this cation on the activity of PEPCK appears untenable. Magnesium is involved in the secretion of insulin, glucagon, epinephrine and corticosterone. These hormones all affect the gluconeogenic enzymes. A change in the circulating level of one or more of these hormones may be responsible for the effects of magnesium depletion on PEPCK.