GLUCONEOGENIC PRECURSORS STIMULATE ACETONE METABOLISM IN ISOLATED MURINE HEPATOCYTES

In our earlier paper (Kalapos et al., Int. J. Biochem. 26, 1069-1079, 1994) we described that the contribution of acetone to net glucose for mation in isolated murine hepatocytes was only possible when alanine w as present. The aim of the present work was to investigate whether the above mentioned phenomenon was specific to alanine. Hepatocytes were prepared from 48 hr-starved mice maintained on untreated or acetone-tr eated drinking water. Glucose production was determined in cells after 30 min incubation with different gluconeogenic substrates using gluco se oxidase/peroxidase method. Glucose formation from glycerol, fructos e, alanine, methylglyoxal, and lactate was increased by the addition o f acetone in hepatocytes prepared from 48 hr-starved animals, while ac etone reduced glucose production in the cells which originated from ac etone pretreated 48 hr-starved mice. However, a higher rate of glucose production from 1 mM pyruvate in combination with 1 mM acetone compar ed with glucose production from 1 mM pyruvate was observed, in hepatoc ytes originated from starved animals without and with acetone pretreat ment glucose formation, expressed in nmol glucose/10(6) cells, was ele vated from 172.3 +/- 21.4 (SEM, n = 5) to 205.3 +/- 29.0 (SEM, n = 5, P < 0.05) and from 164.9 +/- 20.2 (SEM, n = 5) to 195.2 +/- 14.0 (SEM, n = 5, P < P.05), respectively. In summary, the action of acetone on glucose production from gluconeogenic substrates is not restricted to alanine, as a substrate. It is concluded that acetone may play a role in maintenance of hepatic glucose output in ketonemia and may do so by using a wide range of substrates for NADPH + H+ generation which, as a cofactor, is needed for the cytochrome P450s to metabolize acetone. (C) 1996 Elsevier Science Ltd