Adaptive changes in gluconeogenic enzymes in rat liver and kidney during long-term ethanol ingestion

Abstract

Activities of three hepatic and renal gluconeogenic enzymes, phosphoenol-pyruvate carboxykinase (PEP carboxykinase), fructose-1, 6-diphosphatase (FD-Pase), glucose-6-phosphatase (G6Pase), together with plasma immunoreactive insulin (IRI) and glucagon (IRG) concentrations and the main parameters of carbohydrate metabolism, were measured in rats fed on liquid diets in which 36% of the total energy intake was derived from ethanol. Experiments were conducted both on medium fat and high fat (10% and 40% of total energy from fat respectively) diets. Two types of control diet were used, one in which ethanol was replaced by glucose (type I) and one (type II) in which it was replaced by glucose and fat in the same ratio as in the corresponding ethanol diet. PEP carboxykinase and FDPase showed statistically significant ethanol-induced increases (16%–40%) in both the medium fat and high fat diet groups, but the increases in hepatic G6Pase, although qualitatively similar, were not statistically significant. The renal enzyme activities increased to approximately the same extent, the increases varying from 3% to 40% in different groups. No statistically significant differences were found between the animals fed on the two types of control diet. No marked ethanol-induced changes were shown in plasma IRG concentrations, but plasma IRI concentrations tended to be lower in the groups receiving ethanol than in the control groups in both sets of experiments. The results show that the ethanol-induced inhibition of hepatic gluconeogenesis initiates compensatory mechanisms which, in long-term experiments, result in an increase in the maximum activity of the adaptive enzymes of gluconeogenesis both in liver and kidney, probably indicating regulation at the level of the tissue concentration of the enzyme protein. The similarity of the changes in the kidney and liver is suggestive of a common inductor for the gluconeogenic enzymes in both organs. The possible mediators of enzymic adaptation are discussed.