Inhibition of glycogenolysis enhances gluconeogenic precursor uptake by the liver of conscious dogs

We investigated the effect of inhibiting glycogenolysis on gluconeogenesis in 18-h-fasted conscious dogs with the use of intragastric administration of BAY R 3401, a glycogen phosphorylase inhibitor. Isotopic ([3-3H]glucose and [U-14C]alanine) and arteriovenous difference methods were used to assess glucose metabolism. Each study consisted of a 100-min equilibration, a 40-min control, and two 90-min test periods. Endogenous insulin and glucagon secretions were inhibited with somatostatin (0.8 μg ⋅ kg−1 ⋅ min−1), and the two hormones were replaced intraportally (insulin: 0.25 mU ⋅ kg−1 ⋅ min−1; glucagon: 0.6 ng ⋅ kg−1 ⋅ min−1). Drug (10 mg/kg) or placebo was given after the control period. Insulin and glucagon were kept at basal levels in the first test period, after which glucagon infusion was increased to 2.4 ng ⋅ kg−1 ⋅ min−1; BAY R 3401 decreased tracer-determined endogenous glucose production [rate of glucose production (Ra): 14 ± 1 to 7 ± 1 μmol ⋅ kg−1 ⋅ min−1] and net hepatic glucose output (11 ± 1 ...