Open AccessPhospho enol pyruvate Carboxykinase in Cultured Foetal Hepatocytes from the Rat
Author(s) -
STEELE John G.,
MCGRATH Malcolm C.,
YEOH George C. T.,
OLIVER Ivan T.
Publication year - 1980
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1980.tb04404.x
Subject(s) - glucagon , endocrinology , medicine , phosphoenolpyruvate carboxykinase , insulin , gluconeogenesis , hormone , hepatocyte , biology , chemistry , biochemistry , metabolism , enzyme , in vitro
The involvement of glucocorticoids and insulin in the induction of cytosolic P pyruvate carboxykinase was studied in cultured hepatocytes derived from 19‐day foetal rat liver. Dexamethasone did not increase P pyruvate carboxykinase activity, but had a synergistic effect on the induction of the enzyme by N 6 , O 2′ ‐dibutyryladenosine 3′,5′‐monophosphate (Bt 2 cAMP). Insulin partially inhibited the induction of P pyruvate carboxykinase by glucagon, epinephrine or Bt 2 cAMP. The inhibitory effect of insulin was dose‐dependent: significant inhibition was obtained with 0.1 nM insulin. However, the effect of insulin was independent of the dose of glucagon or epinephrine added to the culture medium. The ontogeny of inducibility of P pyruvate carboxykinase by Bt 2 cAMP or hormones was tested in foetal hepatocytes after one day of culture. P pyruvate carboxykinase activity could be induced by epinephrine, glucagon or Bt 2 cAMP in hepatocytes isolated from day‐19, day‐16 or day‐14 foetuses. Similarly, hepatocytes isolated from day‐12 foetal liver were competent to respond to the hormones and Bt 2 AMP by the accumulation of P pyruvate carboxykinase. Binding proteins for adenosine 3′,5′‐monophosphate (cyclic AMP) were demonstrated in the cytosol from hepatocytes isolated from day‐14 and day‐19 foetal liver. The results are discussed in terms of the acquisition during hepatocyte differentiation of the competence to respond to hormonal signals, and the role of hormones in the induction of hepatic P pyruvate carboxykinase at birth.