Studies on hepatic glucose cycles in normal and methylprednisolone-treated dogs

In unanesthetized normal and methyl-prednisolone (MP)-treated dogs the rate of appearance of glucose was measured simultaneously with 2- 3H (RA 2 = hepatic glucose output), 6- 3H (Ra 6 = hepatic glucose production), and 14C-glucose (U) (RaC) as tracers (primed constant rate infusion). The substrate (“futile”) cycle of glucose (SC: gl ⇌ gl-6-P) was obtained from Ra 2 - Ra 6, and Ra 6 - RaC gave the recycling (RC) of radiocarbons. In normal dogs SC and RC represented 13% and 11% of Ra 6, respectively. MP increased SC almost eightfold without altering RC. Infusion of glucagon (increased breakdown of glycogen, inhibition of glycogen synthetase) or mannoheptulose (inhibition of glucokinase) as well as exercise increased SC. MP greatly potentiated the effect causing SC to rise to 20 times the normal base-line. In both groups there was a direct correlation between Ra 6 and SC. Glucose infusion did not alter SC in the controls, but increased it in the MP-treated dogs by suppressing Ra 6 more than Ra 2. It is suggested that the multifunctional character of gl-6-Pase is at least partly responsible for the glucose substrate cycle, using gl-6-P as one of the phosphate donors: gl-6-P + 3H-gl ⇌ 3H-gl-6-P+gl. The activity of this enzyme is greatly elevated by the glucocorticoid, and it can be further enhanced by increasing the availability of gl-6-P by raising Ra 6.