Lack of hepatic “interregulation” during inhibition of glycogenolysis in a canine model

Abstract

It has been proposed that the glycogenolytic and gluconeogenic pathways contributing to endogenous glucose production are interrelated. Thus a change in one source of glucose 6-phosphate might be compensated for by an inverse change in the other pathway. We therefore investigated the effects of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB), a potent glycogen phosphorylase inhibitor, on glucose production in fasted conscious dogs. When dogs were treated acutely with high glucagon, glucose production rose from 1.93 ± 0.14 to 3.07 ± 0.37 mg · kg−1· min−1( P < 0.01). When dogs were treated acutely with DAB in addition to high glucagon infusion, the stimulation of the glycogenolytic rate was completely suppressed. Glucose production rose from 1.85 ± 0.20 to 2.41 ± 0.17 mg · kg−1· min−1( P < 0.05), which was due to the increase in gluconeogenesis from 0.93 ± 0.09 to 1.54 ± 0.08 mg · kg−1· min−1( P < 0.001). In conclusion, infusion of DAB inhibited glycogenolysis; however, the absolute contribution of gluconeogenesis to glucose production was not affected. These results suggest that inhibition of glycogenolysis could be an effective antidiabetic treatment.