Stimulation of gluconeogenesis leads to an increased rate of beta-oxidation in hepatocytes from fasted diabetic but not from fasted normal rats.
We have investigated the effects of imposing an ATP demand, generated by the addition of lactate, on hepatocytes isolated from fasted normal and streptozocin-induced diabetic rats. The stimulation of O2 consumption upon lactate addition was much greater in hepatocytes from diabetic rats, as a result of a lactate-induced stimulation of beta-oxidation that was not observed in control cells. This lactate-induced increment in beta-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 beta-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 beta-oxidation in cells from diabetic animals than in cells from normal rats. The increment in beta-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.
Henly
D C
DC
Department of Medical Biochemistry, School of Medicine, Faculty of Health Sciences, Flinders University of South Australia, Adelaide.
Phillips
J W
JW
Berry
M N
MN
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000968:Antimycin A / Q000031:analogs & derivatives / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005215:Fasting; D005227:Fatty Acids / Q000378:metabolism; D005943:Gluconeogenesis; D007773:Lactates / Q000494:pharmacology; D019344:Lactic Acid; D008099:Liver / Q000378:metabolism*; D008297:Male; D063991:Mitochondrial Trifunctional Protein; D009097:Multienzyme Complexes / Q000378:metabolism; D009840:Oligomycins / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D005227:Fatty Acids; D007773:Lactates; D009097:Multienzyme Complexes; D009840:Oligomycins; C032456:antimycin; D019344:Lactic Acid; D000968:Antimycin A; D000255:Adenosine Triphosphate; D063991:Mitochondrial Trifunctional Protein