Depression of Hepatic Ghiconeogenesis by Acute Lead Administration 1

Abstract

Summary

Male rats were administered either 5 mg lead acetate or sodium acetate iv and then fasted overnight. Gluconeogenesis was assessed both in vivo employing radiotracer as well as chemical conversions of alanine to glucose, and in vitro using isolated hepatocytes. Lead-treated rats had depressions in both ¹⁴C-alanine incorporation into blood glucose and the hyperglycemic response to an alanine load. Isolated hepatocyte gluconeogenesis from either 10 mM alanine, lactate or pyruvate was depressed from 40 to 60% for lead-treated rats as compared to controls; the addition of lead acetate to normal hepatocytes in vitro had no effect on gluconeogenesis. Glucose synthesis from three precursors which do not require a mitochondrial step for conversion to glucose—i.e., fructose, glycerol, and oxaloacetate—was not markedly depressed in hepatocytes from lead-treated rats. Incorporation of ¹⁴C-alanine into both glucose and carbon dioxide were also depressed following lead treatment. These data on hepatic gluconeogenesis support a mitochondrial locus of lead action and suggest that defects in hepatic glucoregulation may play a role in the toxicity of acute lead poisoning.