Effects of manganese deficiency on pyruvate carboxylase and phosphoenolpyruvate carboxykinase activity and carbohydrate homeostasis in adult rats.

The activities of two liver gluconeogenic enzymes, pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase (PEPCK), as well as liver glycogen and plasma glucose, insulin, and glucagon were measured in first- and second-generation, manganese-sufficient (control) and manganese-deficient (Mn-) adult rats. Pyruvate carboxylase activity of first generation male Mn- rats was higher than that of controls in both the fed and fasted states. In contrast, PC activity in second generation male Mn- rats was lower than control levels. In female rats, PC activity was lower than controls in both fed, first- and second-generation Mn- rats; in the fasted state, PC activity was either the same or higher than controls. Phosphoenolpyruvate carboxykinase activity was lower in male first generation Mn- rats than in controls, but there was no difference in PEPCK activity in second-generation animals. Phosphoenolpyruvate carboxylase activity was lower in both fed and fasted Mn- female rats than in controls. Plasma insulin levels were lower in the deficient rats than in controls, whereas plasma glucagon levels were similar. Manganese-deficient rats had higher concentrations of liver glycogen than their controls. These findings provide further evidence that manganese affects carbohydrate homeostasis; however, the response of the animal to manganese deficiency depends on the parameter studied and the timing of the deficiency.