The direct effects of catecholamines on hepatic glucose production occur via alpha(1)- and beta(2)-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 microg x kg(-1) x min(-1)) was infused portally during both test periods, and NE (50 ng x kg(-1) x min(-1)) was infused portally at the start of test period 2. In group 2, beta-blockade with epinephrine (beta-blo+EPI), propranolol (1 microg x kg(-1) x min(-1)) was infused portally during both test periods, and EPI (8 ng x kg(-1) x min(-1)) was infused portally during test period 2. In group 3 (alpha(1)-blo+NE), prazosin (4 microg x kg(-1) x min(-1)) was infused portally during all test periods, and NE (50 and 100 ng x kg(-1) x min(-1)) was infused portally during test periods 2 and 3, respectively. In group 4 (beta(2)-blo+EPI), butoxamine (40 microg x kg(-1) x min(-1)) was infused portally during all test periods, and EPI (8 and 40 ng x kg(-1) x 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 x kg(-1) x 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 x kg(-1) x 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 x kg(-1) x 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.
Chu
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CA
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Sindelar
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DK
Igawa
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K
Sherck
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S
Neal
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DW
Emshwiller
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Cherrington
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AD
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000596:Amino Acids / Q000097:blood; D000818:Animals; D001158:Arteries / Q000502:physiology; D001786:Blood Glucose / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism* / Q000494:pharmacology; D004285:Dogs; D004837:Epinephrine / Q000378:metabolism / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000008:administration & dosage / Q000096:biosynthesis*; D005990:Glycerol / Q000097:blood; D006854:Hydrocortisone / Q000097:blood; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D011169:Portal Vein / Q000502:physiology; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D000596:Amino Acids; D001786:Blood Glucose; D002395:Catecholamines; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D018340:Receptors, Adrenergic, alpha-1; D018343:Receptors, Adrenergic, beta-2; D019344:Lactic Acid; D005934:Glucagon; D005947:Glucose; D005990:Glycerol; D020155:3-Hydroxybutyric Acid; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine