Role of hepatic alpha- and beta-adrenergic receptor stimulation on hepatic glucose production during heavy exercise.
The role of catecholamines in the control of hepatic glucose production was studied during heavy exercise in dogs, using a technique to selectively block hepatic alpha- and beta-adrenergic receptors. Surgery was done > 16 days before the study, at which time catheters were implanted in the carotid artery, portal vein, and hepatic vein for sampling and the portal vein and vena cava for infusions. In addition, flow probes were implanted on the portal vein and hepatic artery. Each study consisted of a 100-min equilibration, a 30-min basal, a 20-min heavy exercise (approximately 85% of maximum heart rate), a 30-min recovery, and a 30-min adrenergic blockade test period. Either saline (control; n = 7) or alpha (phentolamine)- and beta (propranolol)-adrenergic blockers (Blk; n = 6) were infused in the portal vein. In both groups, epinephrine (Epi) and norepinephrine (NE) were infused in the portal vein during the blockade test period to create supraphysiological levels at the liver. Isotope ([3-3H]glucose) dilution and arteriovenous differences were used to assess hepatic function. Arterial Epi, NE, glucagon, and insulin levels were similar during exercise in both groups. Endogenous glucose production (Ra) rose similarly during exercise to 7.9 +/- 1.2 and 7.5 +/- 2.0 mg.kg-1.min-1 in control and Blk groups at time = 20 min. Net hepatic glucose output also rose to a similar rate in control and Blk groups with exercise. During the blockade test period, arterial plasma glucose and Ra rose to 164 +/- 5 mg/dl and 12.0 +/- 1.4 mg.kg-1.min-1, respectively, but were essentially unchanged in Blk. The attenuated response to catecholamine infusion in Blk substantiates the effectiveness of the hepatic adrenergic blockade. In conclusion, these results show that direct hepatic adrenergic stimulation does not participate in the increase in Ra, even during the exaggerated sympathetic response to heavy exercise.
Coker
R H
RH
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Krishna
M G
MG
Lacy
D B
DB
Bracy
D P
DP
Wasserman
D H
DH
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000409:Alanine / Q000097:blood; D000818:Animals; D004285:Dogs; D004837:Epinephrine / Q000097:blood / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005943:Gluconeogenesis / Q000187:drug effects / Q000502:physiology*; D005990:Glycerol / Q000097:blood; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology*; D005082:Physical Exertion / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013997:Time Factors
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D000409:Alanine; D005990:Glycerol; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine