Comparison of the direct and indirect effects of epinephrine on hepatic glucose production.
To determine the extent to which the effect of a physiologic increment in epinephrine (EPI) on glucose production (GP) arises indirectly from its action on peripheral tissues (muscle and adipose tissue), epinephrine was infused intraportally (EPI po) or peripherally (EPI pe) into 18-h-fasted conscious dogs maintained on a pancreatic clamp. Arterial EPI levels in EPI po and EPI pe groups rose from 97 +/- 29 to 107 +/- 37 and 42 +/- 12 to 1,064 +/- 144 pg/ml, respectively. Hepatic sinusoidal EPI levels in EPI po and EPI pe were indistinguishable (561 +/- 84 and 568 +/- 75 pg/ml, respectively). During peripheral epinephrine infusion, GP increased from 2.2 +/- 0.1 to 5.1 +/- 0.2 mg/kg x min (10 min). In the presence of the same rise in sinusoidal EPI, but with no rise in arterial EPI (during portal EPI infusion), GP increased from 2.1 +/- 0.1 to 3.8 +/- 0.6 mg/kg x min. Peripheral EPI infusion increased the maximal gluconeogenic rate from 0.7 +/- 0.4 to 1.8 +/- 0.5 mg/ kg x min. Portal EPI infusion did not change the maximal gluconeogenic rate. The estimated initial increase in glycogenolysis was approximately 1.7 and 2.3 mg/kg x min in the EPI pe and EPI po groups, respectively. Gluconeogenesis was responsible for 60% of the overall increase in glucose production stimulated by the increase in plasma epinephrine (EPI pe). Elevation of sinusoidal EPI per se had no direct gluconeogenic effect on the liver, thus its effect on glucose production was solely attributable to an increase in glycogenolysis. Lastly, the gluconeogenic effects of EPI markedly decreased (60-80%) its overall glycogenolytic action on the liver.
Chu
C A
CA
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615, USA. Chang.An.Chu@MCmail.Vanderbilt.edu
Sindelar
D K
DK
Neal
D W
DW
Allen
E J
EJ
Donahue
E P
EP
Cherrington
A D
AD
D020155:3-Hydroxybutyric Acid; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000322:Adrenergic Agonists / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000596:Amino Acids / Q000032:analysis / Q000097:blood; D000818:Animals; D001794:Blood Pressure; D004032:Diet; D004285:Dogs; D004837:Epinephrine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005227:Fatty Acids / Q000032:analysis / Q000097:blood; D005260:Female; D005934:Glucagon / Q000032:analysis / Q000097:blood; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000096:biosynthesis*; D005990:Glycerol / Q000032:analysis / Q000097:blood; D006003:Glycogen / Q000378:metabolism; D006339:Heart Rate; D006885:Hydroxybutyrates / Q000032:analysis / Q000097:blood; D007328:Insulin / Q000032:analysis / Q000097:blood; D007700:Kinetics; D019344:Lactic Acid / Q000032:analysis / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000032:analysis / Q000097:blood; D010179:Pancreas / Q000378:metabolism
D000322:Adrenergic Agonists; D000596:Amino Acids; D005227:Fatty Acids; D006885:Hydroxybutyrates; D007328:Insulin; D019344:Lactic Acid; D006003:Glycogen; D005934:Glucagon; D005947:Glucose; D005990:Glycerol; D020155:3-Hydroxybutyric Acid; D009638:Norepinephrine; D004837:Epinephrine