Effects of subacute low level lead exposure on glucose homeostasis.

Administration of low levels of lead (0.001, 0.005 and 0.025 micrograms/g/day p.o.) to neonate rats from age three days to eight weeks failed to alter the activities of hepatic glucose-6-phosphatase, fructose-1,6-diphosphatase, pyruvate carboxylase and phosphoenolpyruvate carboxykinase, the four key gluconeogenic enzymes. Administration of lead at a higher dose (0.1 micrograms/g/day p.o.) was also observed to produce no alterations in enzyme activity at eight weeks. However, the higher dose did enhance the activities of fructose-1,6-diphosphatase and phosphoenolpyruvate carboxykinase at age six weeks. Plasma insulin and glucagon were not significantly altered by up to 0.025 micrograms/g exposure to lead until eight weeks of age, although levels of these hormones appear to be slightly dose-responsive tending towards elevated glucagon and decreased insulin levels with increasing lead dosage. At 0.1 micrograms/g/day glucagon was significantly increased at eight weeks. Blood glucose and hepatic glycogen remained unaltered. Blood, hepatic and pancreatic lead levels were unchanged by treatment with lead up to 0.025 micrograms/g/day to eight weeks of age, but there was evidence of lead accumulation in pancreatic tissue whereas levels of the metal in the liver paralleled those in the blood. Significant increases were observed with 0.1 micrograms/g/day lead at six and eight weeks in blood and pancreas. Data are presented which suggest that six week old animals are more influenced by subacute lead exposure than are the eight week old animals, as reflected in some alteration of gluconeogenic enzyme activity in younger rats.