AbstractIn perfused livers from fed rats, rates of glucose production (glycogenolysis) were 133 ± 12 μmol/g/hr. Infusion of 2 μM verapamil into these livers decreased the rates of glucose production significantly to 97 ± 15 μmol/g/hr within 10 min. Conversely, rates of production of lactate plus pyruvate (glycolysis) of 64 ± 6 μmol/g/hr were not significantly altered by verapamil (60 ± 3 μmol/g/hr). When 50 μM verapamil was infused, however, rates of both glycogenolysis and glycolysis were diminished to 56 ± 11 and 43 ± 5 μmol/g/hr, respectively. In perfused livers from fasted rats, infusion of 20 mM fructose increased the rates of production of glucose (gluconeogenesis) significantly from 11 ± 7 to 121 ± 17 μmol/g/hr. These rates reached 138 ± 7 μmol/g/hr upon the simultaneous infusion of verapamil (2 μM). In these livers, fructose also increased rates of production of lactate from 6 ± 2 to 132 ± 11 μmol/g/hr, which were further increased to 143 ± 8 μmol/g/hr when 2 μM verapamil was infused. The results show that calcium‐dependent processes involved in hepatic carbohydrate metabolism respond differently to the calcium channel blocker verapamil. Low concentrations of verapamil inhibited glycogenolysis significantly while having no effect on either glycolysis or gluconeogenesis. These data suggest that these two processes have different sensitivities to changes in intracellular calcium concentrations and/or different sou