COOPERATIVE EFFECT BETWEEN RECOMBINANT MOUSE IL-6 OR RECOMBINANT HUMAN IL-1 AND GLUCAGON ON ALPHA-AMINOISOBUTYRIC-ACID UPTAKE AND PHOSPHOENOLPYRUVATE CARBOXYKINASE ACTIVITY IN CULTURED RAT HEPATOCYTES

alpha-Amino [1-C-14]isobutyric acid ([C-14]AIB) is a non-metabolizable analogue of alanine, the principal amino acid released by muscle in catabolic states and the major gluconeogenic amino acid in the liver. Phosphoenolpyruvate carboxykinase (PEPCK) is a rate-limiting enzyme in gluconeogenesis. Many factors, such as hormones and cytokines, have effect on both uptake of alanine by the liver and the hepatic PEPCK activity. The aim of this study was to evaluate the cooperative effect of recombinant mouse IL-6 (rmIL-6) and recombinant human IL-1 (rhIL-1) with glucagon on [C-14]AIB uptake and PEPCK activity in cultured rat hepatocytes. Our data showed that rmIL-6 and glucagon increased [C-14]- AIB uptake individually in a dose-dependent manner and had a significant additive effect on the uptake in rat hepatocytes. However, rhIL-1 had no effect on [C-14]AIB uptake. Regarding PEPCK, rmIL-6 and rhIL-1 had no effect on the activity of PEPCK in rat hepatocytes. But both rmIL-6 and rhIL-1 significantly inhibited the stimulative effect of glucagon on hepatic PEPCK activity of the rats.