Metabolic interactions of glucose, acetoacetate and adrenaline in rat submaxillary gland in vitro.
1. The metabolic interactions between glucose, acetoacetate and adrenaline were studied in submaxillary-gland slices. 2. Acetoacetate (2.5 mM) inhibited glucose removal by 22% and entry of glucose carbon into the tricarboxylic acid cycle by 54%. 3. Acetoacetate caused an increase in (glucose 6-phosphate) together with an increase in (citrate), a finding that suggests that the phosphofructokinase step might be inhibited by the elevated (citrate). Support for this suggestion was obtained in experiments in which fluoracetate was used to elevate (citrate). 4. A further site of action of acetoacetate at the pyruvate dehydrogenase step was suggested by an increase in the lactate+pyruvate pool, and the finding that pyruvate removal and (3-14C)pyruvate oxidation were inhibited by acetoacetate. 5. Adrenaline, a stimulator of secretion by this tissue, increased glucose removal by 25%. Adrenaline increased glucose removal to the same extent when acetoacetate was also present in the incubation medium. In both cases the increase was accompanied by a fall in (glucose 6-phosphate). 6. Adrenaline also overcame the inhibition of pyruvate removal caused by acetoacetate. 7. The tissue (ATP) decreased by about 50% on addition of adrenaline, and a similar fall was observed in vivo after adrenergic stimulation by isoproterenol. 8. Omission of Ca-2+ from the medium prevented the fall in (glucose 6-phosphate) and (ATP) caused by adrenaline, although adrenaline was still able to stimulate glucose removal. The inhibitory effect of acetoacetate on gluocse removal was reversed by adrenaline, but there was no stimulation above the control rates. Inhibition of pyruvate removal by acetoacetate was not overcome by adrenaline in the absence of Ca-2+. 9. Dibutyryl cyclic AMP had no effect on glucose removal or on (ATP). 10. Possible mechanisms by which adrenaline can bring about its metabolic effects are discussed.
D000090:Acetoacetates / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D003994:Bucladesine; D002951:Citrates / Q000032:analysis / Q000378:metabolism; D002952:Citric Acid Cycle; D004837:Epinephrine / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D005958:Glucosephosphates / Q000032:analysis; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010732:Phosphofructokinase-1 / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D011773:Pyruvates / Q000032:analysis / Q000378:metabolism; D051381:Rats; D013363:Submandibular Gland / Q000032:analysis / Q000378:metabolism*
D000090:Acetoacetates; D002951:Citrates; D005958:Glucosephosphates; D011768:Pyruvate Dehydrogenase Complex; D011773:Pyruvates; D003994:Bucladesine; D000255:Adenosine Triphosphate; D010732:Phosphofructokinase-1; D005947:Glucose; D004837:Epinephrine