Effect of glucagon on hepatic energy charge and arterial ketone body ratio in normal rabbits.

Abstract

Glucagon has been regarded as a hepatotrophic factor, although it is also known to stimulate energy-consuming reactions in the liver, such as gluconeogenesis and ureogenesis. To clarify the effect of glucagon on the hepatic energy metabolism, the changes in arterial ketone body ratio, which reflects the hepatic mitochondrial redox state [( NAD+]/[NADH]), as well as those in energy charge and mitochondrial oxidative phosphorylation of the liver after IV glucagon injection were studied in normal rabbits. Arterial ketone body ratio decreased significantly from 1.04 +/- 0.08 to 0.61 +/- 0.11 (mean +/- SEM; P less than 0.01) within 30 minutes after glucagon injection. Hepatic energy charge also decreased from 0.883 +/- 0.014 to 0.789 +/- 0.014 (P less than 0.01) at 30 minutes, whereas mitochondrial phosphorylation rate inversely increased from 38.4 +/- 9.5 to 87.3 +/- 9.7 (nanomoles adenosine triphosphate per milligram mitochondrial protein per minute; P less than 0.01) at 30 minutes. Arterial ketone body ratio and energy charge were subsequently restored to the initial values at 60 minutes and 2 hours, respectively. The present study suggests that glucagon causes an increase in energy expenditure in the liver that results in a transient decrease in hepatic energy charge accompanied by a decrease in arterial ketone body ratio.