GLUCAGON INCREASES URINARY OXALATE EXCRETION IN THE GUINEA-PIG

Factors that influence hepatic oxalate synthesis are poorly defined. H ormones are important regulators of hepatic metabolism and could poten tially be involved. The effects of hyperglucagonemia were examined in guinea pigs injected with either saline or pharmacological doses of gl ucagon for 4 days. Glucagon treatment increased mean urinary oxalate e xcretion by 77% in male and 34% in female animals. The levels of hepat ic peroxisomal enzymes involved in oxalate synthesis declined with glu cagon treatment, but experiments with isolated peroxisomes indicated t hat oxalate synthesis in vitro was unaffected. Glucagon decreased hepa tic alanine levels by 66%, lactate by 69%, and pyruvate by 73%, but gl ycolate and glyoxylate levels were unaffected. This decrease in alanin e would substantially lower the activity of alanine-to-glyoxylate amin otransferase activity in vivo and make more glyoxylate available for o xalate synthesis. The decrease in lactate and pyruvate concentrations would stimulate the enzymatic conversion of glyoxylate to oxalate and may account for the increase in oxalate synthesis without an increase in glyoxylate concentration. These results demonstrate that hepatic ox alate synthesis is influenced by metabolic changes and that alteration s in hepatic alanine, lactate, and pyruvate concentrations may be impo rtant elements.