Dc. Henly et al., STIMULATION OF GLUCONEOGENESIS LEADS TO AN INCREASED RATE OF BETA-OXIDATION IN HEPATOCYTES FROM FASTED DIABETIC BUT NOT FROM FASTED NORMAL RATS, Biochimica et biophysica acta (G). General subjects, 1244(1), 1995, pp. 92-98
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 cons
umption upon lactate addition was much greater in hepatocytes from dia
betic rats, as a result of a lactate-induced stimulation of beta-oxida
tion that was not observed in control cells. This lactate-induced incr
ement in beta-oxidation was extremely sensitive to inhibition by low l
evels of a number of inhibitors of energy transduction, implying that
the increment was tightly coupled to ATP synthesis. Such sensitivity o
f the beta-oxidative pathway to the addition of similar low concentrat
ions of these inhibitors was not seen in control cells. Inhibitors of
the gluconeogenic pathway were also more effective in decreasing beta-
oxidation in cells from diabetic animals than in cells from normal rat
s. The increment in beta-oxidation was not accompanied by increased ra
tes of glucose synthesis, fatty acid esterification or ureogenesis. We
propose that it may be associated with higher rates of glucose cyclin
g in cells from diabetic rats.