NET GLUCOSE-PRODUCTION FROM ACETONE IN ISOLATED MURINE HEPATOCYTES - THE EFFECT OF DIFFERENT PRETREATMENTS OF MICE

1. To evaluate the condition under which net glucose production from a cetone, added as sole substrate, occurs different pretreatments of mic e, in combination with starvation, were used; (i) acetone pretreatment (acetone is a known inducer of cytochrome P-450 isozymes involved in this pathway), (ii) fructose pretreatment (to induce NADPH + H+ genera ting enzymes) or (iii) their combination. 2. There was net glucose for mation from acetone only in that case, when the cells were prepared fr om 48 hr fasted animals pretreated with both acetone and fructose. How ever, using 2-C-14-acetone, incorporation of C-14-carbon into glucose could be detected in all the cases and, at the same time, acetone was without any effect on protein synthesis. 3. The addition of acetone in creased gluconeogenesis from alanine in almost all the cases. The only exception from this general rule was that the case, when hepatocytes were prepared from acetone pretreated 48 hr starved mice where, instea d of the elevation of glucose formation, a decrease of that was caused by acetone. 4. Acetone decreased C-14-carbon incorporation into gluco se from C-14-(U)-alanine added at saturating concentration in hepatocy tes prepared from starved mice. 5. Similarly to acetone there was no n et glucose formation from acetol either when added alone, however, it enhanced gluconeogenesis from alanine at non-saturating concentrations of the amino acid. 6. Methylglyoxal proved gluconeogenic in all the c ases. 7. It is concluded that net glucose formation from acetone as so le substrate occurs only under those conditions which are far from a p hysiological situation, however, when gluconeogenesis from another sub strate takes place, acetone can contribute to net glucose formation in hepatocytes prepared from fasted mice.