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

Abstract

The role of α- and β-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 [α-blockade with norepinephrine (α-blo+NE)], phentolamine (2 μg · 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. In group 2, β-blockade with epinephrine (β-blo+EPI), propranolol (1 μg · 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. In group 3 (α1-blo+NE), prazosin (4 μg · 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(β2-blo+EPI), butoxamine (40 μg · 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 α- or α1-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 mg · kg−1 · min−1. In the presence of β- or β2-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 α1- and β2-adrenergic receptors, respectively.