Effect of glucagon on lipids and glucose in normal and eviscrated rats and on isolated perfused rat livers

Abstract

Part 1 (in vivo): Concentrations of free fatty acids (FFA), cholesterol, amino nitrogen, glucose, and ketones in the blood, and total fat content of the liver were measured at regular intervals over a period of nine hours after the administration of 2 mg. of glucagon to male rats (fasted 48 hours prior to use). The amounts of all these metabolites in the blood, with the exception of glucose, decreased, as did the liver lipid. There was no immediate hyperglycemic effect of glucagon in the fasted animals, although a small but significant elevation in blood glucose occurred after nine hours. The hormone produced qualitatively similar changes over a six-hour period in fed rats, in which plasma total esterified fatty acids (TEFA), but not liver lipids, were measured as well. These changes persisted when the blood glucose concentrations were the same as in the controls, after a presumed period of hyperglycemia. Concentrations of lipids and amino nitrogen in the blood of eviscer-rated functionally hepatectomized rats were not significantly affected by the administration of glucagon. Part 2 (in vitro): In the isolated perfused livers, glucagon caused an increase in the perfusate blood glucose, a reduction in the increase in the cholesterol, and a decrease in the FFA concentrations. These changes are statistically highly significant. The addition of glucagon did not cause a signficant change in the TEFA in the perfusate, but did result in a significant fall in the liver TEFA content. The decrease in the amounts of lipids in blood of glucagon treated rats, and in the perfusate of isolated perfused rat livers, has been interpreted as evidence that the hormone inhibits hepatic synthesis of cholesterol and TEFA, and increases hepatic consumption of FFA, the latter possibly being due to increased FFA oxidation.