The direct effects of catecholamines on hepatic glucose production occur via α1- and β2-receptors in the dog

The role of alpha- and beta-adrenergic receptor subtypes in mediating the actions of catecholamines on hepatic glucose production (HGP) was determined in sixteen 18-h-fasted conscious dogs maintained on a pancreatic clamp with basal insulin and glucagon. The experiment consisted of a 100-min equilibration, a 40-min basal, and two 90-min test periods in groups 1 and 2, plus a 60-min third test period in groups 3 and 4. In group 1 [alpha-blockade with norepinephrine (alpha-blo+NE)], phentolamine (2 mu g.kg(-1).min(-1)) was infused portally during both test periods, and NE (50 ng.kg(-1).min(-1)) was infused portally at the start of test period 2. Ingroup 2, beta-blockade with epinephrine (beta-blo+EPI), propranolol (1 mg.kg(-1).min(-1)) was infused portally during both test periods, and EPI (8 ng.kg(-1).min(-1)) was infused portally during test period 2. Ingroup 3 (alpha(1)-blo+NE), prazosin (4 mu g.kg(-1).min(-1)) was infused portally during all test periods, and NE (50 and 100 ng.kg(-1).min(-1)) was infused portally during test periods 2 and 3, respectively. In group 4 (beta(2) -blo+EPI), butoxamine (40 mu g.kg(-1).min(-1)) was infused portally during all test periods, and EPI (8 and 40 ng.kg(-1).min(-1)) was infused portally during test periods 2 and 3, respectively. In the presence of alpha- or alpha(1)-adrenergic blockade, a selective rise in hepatic sinusoidal NE failed to increase net hepatic glucose output (NHGO). In a previous study, the same rate of portal NE infusion had increased NHGO by 1.6 +/- 0.3 mu g . kg (-1) . min (-1). In the presence of beta- or beta(2)-adrenergic blockade, the selective rise in hepatic sinusoidal EPI caused by EPI infusion at 8 ng.kg(-1).min(-1) also failed to increase NHGO. In a previous study, the same rate of EPI infusion had increased NHGO by 1.6 +/- 0.4 mg.kg(-1).min(-1). In conclusion, in the conscious dog, the direct effects of NE and EPI on HGP are predominantly mediated through alpha(1) - and beta(2)-adrenergic receptors, respectively.