Glucocorticoid hormones have a permissive role in the phosphorylation of L-type pyruvate kinase by glucagon.

The incorporation of [32P]phosphate into L-type pyruvate kinase in response to glucagon was studied in hepatocytes isolated from control and adrenalectomized rats. In control cells, pyruvate kinase phosphorylation was maximally stimulated by 210% by glucagon. Adrenalectomy reduced both the basal extent of phosphorylation and the response to glucagon to 25% of those measured in control hepatocytes. This impaired pyruvate kinase phosphorylation was associated with altered kinetic properties of L-type pyruvate kinase. Glucagon injected in vivo (1 mg/kg) into adrenalectomized rats did not increase the substrate-co-operativity of L-type pyruvate kinase. These results suggest a molecular basis for the well-recognised glucocorticoid hormone-dependence for the stimulation by glucagon of hepatic gluconeogenesis. Further effects of this defective enzyme regulation on hepatic metabolism are suggested by the observation that adrenalectomy abolished the ability of glucagon to inhibit hepatic fatty acid biosynthesis both in vivo and in isolated hepatocytes.