Lack of hepatic "interregulation" during inhibition of glycogenolysis in acanine model

It has been proposed that the glycogenolytic and gluconeogenic pathways con tributing 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 inhib itor, on glucose production in fasted conscious dogs. When dogs were treate d 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 gly cogenolytic 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 glycogeno lysis; however, the absolute contribution of gluconeogenesis to glucose pro duction was not affected. These results suggest that inhibition of glycogen olysis could be an effective antidiabetic treatment.