A physiologic increase in brain glucagon action alters the hepatic gluconeogenic glycogenolytic ratio but not glucagon's overall effect on glucose production

The study aimed to determine if central glucagon action plays a physiologic role in regulating HGP. The extraction rate of glucagon across the head was high, and hypothalamic cAMP increased 2-fold, in proportion to the exposure of the brain to increased glucagon, but HGP was not reduced by the increase in brain glucagon signaling, as suggested previously. CNS glucagon action reduced circulating free fatty acids and glycerol, and this was associated with a modest reduction in net hepatic gluconeogenic flux. However, offsetting autoregulation by the liver prevented a change in HGP. Thus, while physiologic engagement of the brain by glucagon can alter hepatic carbon flux, it does not appear to be responsible for the transient fall in HGP following the stimulation of HGP during a square wave rise in glucagon.