To assess the effects of α- and β-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 α- and β-receptors, resulting in plasma NE concentrations of 1.5 ± 0.19 ng/ml; group 2 (n = 7) received NE plus β-blockade; group 3 (n = 7) NE plus α-blockade; group 4 (n = 6) NE plus α- and β-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 μmol · kg−1 · min−1 (P < .01) in saline controls and in an increase in plasma free fatty acids (FFAs) to 1120 ± 102 vs. 526 ± 115 μM (P < .01) in controls. α-Blockade during NE infusion enhanced the lipolytic effect of NE, because plasma FFA increased to 1981 ± 204 vs. 1301 ± 146 μ after 45 min (P < .002), and the ketogenic effect was augmented (14.3 ± 1.7 vs. 5.6 ± 0.9 μmol · kg1 · min−1) after 60 min (P < .001). In contrast, β-blockade abolished the ketogenic and lipolytic effects of NE to those observed in saline controls. Combined α- and β-blockade during NE infusion was without significant effect on ketone body kinetics and plasma FFA. The results indicate that modulation of circulating FFA concentrations plays a predominant role in the acute and α- and β- adrenergic regulation of ketone body production in humans. Because plasma NE concentrations achieved in this study were similar to those observed in severe stress and in diabetic ketoacidosis, the data suggest that in these conditions the lipolytic and ketogenic effects of NE result from β-adrenergic timulation, which is restrained in part by α-adrenergic inhibition.
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Original Articles|
April 01 1989
Contribution of α- and β-Receptors to Ketogenic and Lipolytic Effects of Norepinephrine in Humans
Ulrich Keller;
Ulrich Keller
Departments of Medicine and Research, University Hospital
Basel, Switzerland
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Markus Weiss;
Markus Weiss
Departments of Medicine and Research, University Hospital
Basel, Switzerland
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Werner Stauffacher
Werner Stauffacher
Departments of Medicine and Research, University Hospital
Basel, Switzerland
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Address correspondence and reprint requests to Dr. Ulrich Keller, Department of Internal Medicine, Kantonspital, CH 4031 Basel, Switzerland.
Diabetes 1989;38(4):454–459
Article history
Received:
June 06 1988
Revision Received:
October 31 1988
Accepted:
October 31 1988
PubMed:
2538376
Citation
Ulrich Keller, Markus Weiss, Werner Stauffacher; Contribution of α- and β-Receptors to Ketogenic and Lipolytic Effects of Norepinephrine in Humans. Diabetes 1 April 1989; 38 (4): 454–459. https://doi.org/10.2337/diab.38.4.454
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