Manganese effects on gluconeogenesis.

Manganese (Mn2+) does not significantly increase gluconeogenesis from lactate (10 mM) plus pyruvate (1 mM) in hepatocytes from fasted rats. In hepatocytes not treated with Mn2+, glucagon (1 microM) and epinephrine (10 microM) at these optimal concentrations both stimulate gluconeogenesis from lactate/pyruvate (10:1), but the hormonal effects are not additive. In the presence of Mn2+ the hormonal effects are slightly larger, and the effects of glucagon (1 microM) and epinephrine (10 microM) become nearly completely additive. Mn2+ increases the specific activity of glucose formed from lactate plus NaH14CO3 by nearly 20%. The increase may be attributed to an increased exchange reaction of either pyruvate carboxylase or phosphoenolypyruvate carboxykinase, suggesting that one of these may be markedly stimulated by Mn2+, the increased exchange reaction possibly signifying an approach toward "near equilibrium" status.