Deborah L. Baly

Metabolic Effects of High Doses of Manganese in Rats

The effects of acute manganese (Mn) toxicity on tissue manganese concentrations and on plasma glucose levels were investigated in adult male Sprague-Dawley rats. Manganese injection in all tissues analyzed was reflected by a significant increase in Mn concentration that was transitory. Changes in the molecular localization of Mn in liver following injection include both increases in protein-bound Mn and low molecular weight Mn complexes. A rapid, dose-responsive rise in blood glucose followed Mn injection, whereas circulating insulin levels decreased after injection. These data show that acute changes in tissue Mn levels can have a pronounced effect on carbohydrate metabolism.

Effects of high doses of manganese on carbohydrate homeostasis

The effects of manganese (Mn) toxicity on carbohydrate homeostasis was examined in Sprague-Dawley and Osborne-Mendel rats. Mn injection was followed by increases in Mn concentration in both liver and pancreas. Concentrations of Mn in the pancreas increased more rapidly than in the liver. Plasma insulin levels decreased, plasma glucose levels increased, and a spike in glucagon concentration was observed following Mn injection. Increases in blood glucose in response to Mn injection were also observed in 24- and 48-h fasted rats, although the magnitude of the increase was less than that observed in fed rats. Both strains of rats appeared to respond similarly to Mn injection. The present studies demonstrate that acute Mn injection can affect glucose homeostasis. These effects may be mediated through altered endocrine pancreatic function.

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.