Influence of thyroid state on the effects of glycerol on gluconeogenesis and energy metabolism in perfused rat liver

Abstract

The regulation of gluconeogenesis from lactate (1 mM) and glycerol (2 mM) was investigated in livers from 48 h fasting hypo-, eu- and hyperthyroid rats using the non-recirculating perfusion technique. 1. 1. The rate of gluconeogenesis from glycerol was largely determined by the rate of glycerol uptake which (expressed as μmol/min per g liver) in near steady state was 1.6 in hyperthyroid livers, 1.3 in euthroid livers and 0.8 in hypothyroid livers. However, the initial rate of glycerol uptake was about 1.5 μmol/ min per g liver in all three thyroid states, and the activity of glycerol kinase was identical in all three thyroid states. The inhibition of glycerol uptake in eu- and hypothyroid livers could be explained by competitive inhibition of the glycerol kinase by L-glycerol-3-phosphate. The rate of glycerol uptake in hyperthyroid livers showed no gradual inhibition with time, and did not conform to the model which could describe the kinetics of glycerol uptake in eu- and hypothyroid livers. 2. 2. The rate of gluconeogenesis from lactate was low in hypothyroid livers, and after addition of glycerol to the medium hypothyroid livers released lactate. In eu- and hyperthyroid livers the rate of lactate uptake was identical as was the rate of glucose release when no glycerol was present in the medium. After addition of glycerol to the medium the rate of lactate uptake showed an increase in hyperthyroid livers, whereas the rate of lactate uptake was decreased by glycerol in euthyroid livers. 3. 3. Calculations on changes in ATP consumption due to glycerol uptake and to glycerol-induced changes in lactate uptake as compared to the glycerol-induced changes in oxygen uptake did not suggest any uncoupling of oxidative phosphorylation in the hyperthyroid state.