Stimulation of gluconeogenesis leads to an increased rate of β-oxidation in hepatocytes from fasted diabetic but not from fasted normal rats

Abstract

We have investigated the effects of imposing an ATP demand, generated by the addition of lactate, on hepatocytes isolated from fasted normal and streptozotocin-induced diabetic rats. The stimulation of O 2 consumption upon lactate addition was much greater in hepatocytes from diabetic rats, as a result of a lactate-induced stimulation of β-oxidation that was not observed in control cells. This lactate-induced increment in β-oxidation was extremely sensitive to inhibition by low levels of a number of inhibitors of energy transduction, implying that the increment was tightly coupled to ATP synthesis. Such sensitivity of the β-oxidative pathway to the addition of similar low concentrations of these inhibitors was not seen in control cells. Inhibitors of the gluconeogenic pathway were also more effective in decreasing β-oxidation in cells from diabetic animals than in cells from normal rats. The increment in β-oxidation was not accompanied by increased rates of glucose synthesis, fatty acid esterification or ureogenesis. We propose that it may be associated with higher rates of glucose cycling in cells from diabetic rats.