Insulin and glucagon regulate cytosolic phosphoenolpyruvate carboxykinase (GTP) mRNA in rat liver.
Insulin causes a 7-10-fold decrease of both the mRNA that codes for rat hepatic phosphoenolpyruvate carboxykinase (mRNAPEPCK) and of PEPCK synthesis, provided the animals are made diabetic and fed chow. mRNAPEPCK, measured either by in vitro translation or cDNA hybridization, decreases with a half-time of 30-60 min after insulin treatment. This coordinant decrease, which approximates the half-life of mRNAPEPCK measured in a variety of situations, suggests that insulin acts by decreasing mRNAPEPCK production, and that the hormone does not alter the activity of a fixed amount of this RNA, or enhance its degradation. Glucagon results in a ninefold induction of mRNAPEPCK. Half-maximal induction occurs with doses between 20-75 micrograms/100 g body wt and occurs within 30-45 min. Maximal induction requires 150 micrograms/100 g body wt and occurs about 80 min after a single glucagon injection. N6,O2'-dibutyryl cAMP and a cAMP analogue that is not metabolized, 8-(4-chlorophenyl-thio)cAMP, induce mRNAPEPCK as effectively as glucagon and with similar kinetics. Since sodium butyrate, adenosine, and dibutyryl cGMP are ineffective inducers, cAMP appears to be the active agent in the hepatocyte.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005934:Glucagon / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats
D007328:Insulin; D012333:RNA, Messenger; D003994:Bucladesine; D005934:Glucagon; D000242:Cyclic AMP; D010729:Phosphoenolpyruvate Carboxykinase (GTP)