Acute regulation of hepatic glutathione S-transferase by insulin and glucagon.
The intravenous administration of insulin plus glucose in anesthetized rats caused, within 30 min, an increase of about 56% in hepatic cytosolic glutathione S-transferase (GST) activity, but it did not affect the microsomal enzyme. The injection of glucagon resulted, at the same time, in a 43% drop in the hepatic cytosolic GST, without affecting the microsomal GST. The insulin-dependent increase in cytosolic GST activity was abolished by the pretreatment of the animals with an inhibitor of protein synthesis (cycloheximide). A kinetic analysis revealed a non-competitive inhibition caused by glucagon upon the cytosolic enzyme. In addition, the presence of insulin did not interfere with the effectiveness of glucagon, and vice versa. We propose that: (1) the effect of insulin on hepatic cytosolic GST activity requires protein synthesis; (2) glucagon produces an inhibition of hepatic cytosolic GST, which could be mediated by cytosolic effectors such as adenosine 3'-5'-cyclic monophosphate (cAMP); (3) the effects of glucagon and insulin were not mutually exclusive; (4) hepatic microsomal GST is regulated by different mechanism(s).
Carrillo
M C
MC
Instituto de Fisiologia Experimental, Facultad de Ciencias Bioquimicas y Farmaceúticas, Universidad Nacional de Rosario, Argentina.
Monti
J A
JA
Favre
C
C
Carnovale
C E
CE
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D005934:Glucagon / Q000008:administration & dosage / Q000502:physiology*; D005982:Glutathione Transferase / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000008:administration & dosage / Q000502:physiology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D007328:Insulin; D003994:Bucladesine; D005934:Glucagon; D003513:Cycloheximide; D000242:Cyclic AMP; D005982:Glutathione Transferase