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Am J Physiol Endocrinol Metab 279: E463-E473, 2000;
0193-1849/00 $5.00
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Vol. 279, Issue 2, E463-E473, August 2000

The direct effects of catecholamines on hepatic glucose production occur via alpha 1- and beta 2-receptors in the dog

Chang An Chu, Dana K. Sindelar, Kayano Igawa, Stephanie Sherck, Doss W. Neal, Maya Emshwiller, and Alan D. Cherrington

Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

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 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, beta -blockade with epinephrine (beta -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 (alpha 1-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 (beta 2-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 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 mg · 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.

adrenergic receptor; hepatic glucose production; glycogenolytic rate


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