The effects of stress and injury on the activity of phosphoenolpyruvate carboxykinase in the liver of the rat.
The effects of stress (diethyl ether anaesthesia for 4-8 min, or intravenous injection of 0.05 ml of a dimethyl sulphoxide/water mixture) and of a scald injury given under ether anaesthesia on hepatic PEPCK (phosphoenolpyruvate carboxykinase, EC 4.1.1.32) were studied in the post-absorptive rat. Injury raised PEPCK activity by about 70% in 2 h and by over 100% in 4 h, over three times as fast as in animals that had only been handled (controls). The two stresses, both of types commonly imposed in animal experiments, had almost as much effect as injury for the first 2 h, although much less thereafter. The roles of sympathetic stimulation and corticosterone in mediating these rises were studied by using alpha beta-blockers and trilostane respectively as inhibitors. (Trilostane only decreased corticosterone concentrations to a little above control values.) The ether-induced increase was somewhat decreased by alpha beta-blockade, but was only eliminated by combined alpha beta-blockade and trilostane. After injury, however, PEPCK synthesis was unaffected by either alpha beta-blockade or trilostane, although it was decreased by their combined action; and it seems that either corticosterone or sympathetic stimulation was sufficient to stimulate PEPCK synthesis maximally. Stimulation by corticosterone was much greater than reported previously by others, for reasons that are discussed. Sympathetic stimulation may have been mediated by glucagon and cyclic AMP, since injury raised portal glucagon concentrations, and stress and injury raised those of hepatic cyclic AMP. PEPCK synthesis was, however, stimulated despite increases in portal insulin concentration, and was not related to the [insulin]/[glucagon] ratio. Thus stress and injury over-rode normal control mechanisms.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002056:Burns / Q000201:enzymology*; D003345:Corticosterone / Q000097:blood; D000242:Cyclic AMP / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005934:Glucagon / Q000097:blood; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008099:Liver / Q000201:enzymology*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013312:Stress, Physiological / Q000201:enzymology*
D001786:Blood Glucose; D007328:Insulin; D007773:Lactates; D008112:Liver Glycogen; D019344:Lactic Acid; D005934:Glucagon; D000242:Cyclic AMP; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D003345:Corticosterone; D004121:Dimethyl Sulfoxide