Contribution of alpha- and beta-receptors to ketogenic and lipolytic effects of norepinephrine in humans.
To assess the effects of alpha- and beta-adrenergic-receptor activation on ketone body kinetics and lipolysis in humans, five groups of overnight-fasted subjects were studied. Group 1 (n = 7) received norepinephrine (NE) to activate alpha- and beta-receptors, resulting in plasma NE concentrations of 1.5 +/- 0.19 ng/ml; group 2 (n = 7) received NE plus beta-blockade; group 3 (n = 7) NE plus alpha-blockade; group 4 (n = 6) NE plus alpha- and beta-blockade; and group 5 (n = 6) saline. Plasma insulin and glucagon concentrations were maintained constant by infusion of somatostatin with insulin and glucagon replacements. Infusion of NE for 170 min resulted in an increase in total ketone body production ([3-14C]acetoacetate infusions) to 8.5 +/- 1.3 vs. 3.9 +/- 0.6 mumol.kg-1.min-1 (P less than .01) in saline controls and in an increase in plasma free fatty acids (FFAs) to 1120 +/- 102 vs. 526 +/- 115 microM (P less than .01) in controls. alpha-Blockade during NE infusion enhanced the lipolytic effect of NE, because plasma FFA increased to 1981 +/- 204 vs. 1301 +/- 146 microM after 45 min (P less than .002), and the ketogenic effect was augmented (14.3 +/- 1.7 vs. 5.6 +/- 0.9 mumol.kg-1.min-1) after 60 min (P less than .001). In contrast, beta-blockade abolished the ketogenic and lipolytic effects of NE to those observed in saline controls. Combined alpha- and beta-blockade during NE infusion was without significant effect on ketone body kinetics and plasma FFA.(ABSTRACT TRUNCATED AT 250 WORDS)
Keller
U
U
Department of Medicine, University Hospital, Basel, Switzerland.
Weiss
M
M
Stauffacher
W
W
D000328:Adult; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D007657:Ketone Bodies / Q000097:blood*; D007700:Kinetics; D007773:Lactates / Q000097:blood; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D012016:Reference Values
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007657:Ketone Bodies; D007773:Lactates; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D005934:Glucagon; D009638:Norepinephrine; D010646:Phentolamine