Effects of growth hormone on pyruvate dehydrogenase activity in intact rat liver and in isolated hepatocytes: comparison with insulin.
The effects of growth hormone and insulin on the activity of pyruvate dehydrogenase were examined in the rat, both in vivo and in isolated hepatocytes. Liver mitochondria isolated from rats killed from five to 45 minutes after injection of 50 micrograms/100 g human growth hormone (hGH) or 25 micrograms/100 g insulin displayed a significant increase in the activity of basal pyruvate dehydrogenase (38% and 48% above control at ten minutes, respectively). These changes probably result from the conversion of the phosphorylated form to the nonphosphorylated form of pyruvate dehydrogenase since total enzyme activity was unaffected. Treatment of isolated hepatocytes by hGH or insulin also led to an increase in pyruvate dehydrogenase activity which was maximal (25% above control value) at 15 minutes. Later, activation progressively decreased and was no longer detectable at 60 minutes. The concentrations of hGH or insulin required for maximal activation were 100 nmol/L and 20 nmol/L, respectively, and the concentration required for half-maximal stimulation was 2 nmol/L for both hormones. The effects of 100 nmol/L hGH and 100 nmol/L insulin on pyruvate dehydrogenase activity were not additive. Basal pyruvate dehydrogenase activity in hepatocytes exhibited linear kinetics; hGH or insulin increased the Vmax of the enzyme without changing its Km and did not affect the Vmax of the total enzyme activity. It is concluded that growth hormone is as potent and as efficient as insulin in its ability to stimulate the activity of liver pyruvate dehydrogenase, and thus may be a physiological activator of this enzyme.
Clot
J P
JP
Inserm U30, Hôpital des Enfants Malades, Paris, France.
Benelli
C
C
de Gallé
B
B
Postel-Vinay
M C
MC
Durand
D
D
Desbuquois
B
B
D000818:Animals; D002478:Cells, Cultured; D013006:Growth Hormone / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D012016:Reference Values
D007328:Insulin; D011768:Pyruvate Dehydrogenase Complex; D013006:Growth Hormone