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Effect of Epinephrine on the Relationship Between Nonesterified Fatty Acid Availability and Ketone Body Production in Postabsorptive Man: Evidence for a Hepatic Antiketogenic Effect of Epinephrine^*

INSERM U.197, Faculté de Médecine Alexis Carrel Lyon, France
Service de Radioanalyse, Hôpital Neurocardiologique (R.C.) Bron, France

Address requests for reprints to: M. Beylot, INSERM U. 197, Faculté de Médecine Alexis Carrel, rue G. Paradin, 69372 Lyon Cedex 08, France.

The effect of epinephrine (EPI) on the transformation of nonesterified fatty acids (NEFA) into ketone bodies (KB) in normal subjects was determined by measuring simultaneously NEFA ([1-¹³C] palmitic acid) and KB ([3-¹³C]- or [3,4-¹³C₂]acetoacetate) kinetics at different NEFA levels in the presence of basal (control test) or increased (EPI infusion test) EPI concentrations. During the control test the initial (postabsorptive state) concentrations and turnover rates of NEFA and KB were 476 ± 47 (±SEM) and 4.30 ± 0.17 µmol kg^–1 min^–1 (NEFA) and 126 ± 17 and 2.49 ± 0.07 µmol kg^–1 min^–1 (KB). The fraction of NEFA converted into KB was between 11.5–14.6%. Raising NEFA levels to about 650 µmol L^–1 (iv infusion of a triglyceride emulsion) resulted in an increase in this fraction to between 26–30.3% (P < 0.01). When NEFA concentrations were next abruptly raised to high levels (near 3 mmol L^–1) by heparin injection this fraction returned to near the initial values (15–19.2%). During the EPI infusion test the initial (postabsorptive) concentrations and turnover rates of NEFA and KB as well as the fraction of NEFA converted into KB (10.5–11.5%) were comparable to the initial values of the control test. Intravenous infusion of EPI (10 ng kg^–1 min^–1) raised NEFA between 600 and 750 µmol L^–1, comparable to values during the triglyceride test, but the fraction of NEFA converted into KB remained between 8.2–12% (P < 0.05 vs. control test); when NEFA then were raised to even higher values (near 2.5 mmol L^–1) by the infusion of a triglyceride emulsion and the injection of heparin, this fraction decreased to between 4–8% (P < 0.05 vs. initial values of the EPI test and P < 0.05 vs. the control test). In conclusion, 1) the fraction of NEFA converted into KB appears to depend in part on the NEFA concentration; and 2) the net effect of EPI infusion was to decrease the fraction of NEFA converted into KB.

^* Presented in part at the 22nd Annual Meeting of the European Association for the Study of Diabetes, September 16-20, 1986, Rome, Italy. This work was supported in part by INSERM (Reseau de Recherche Clinique 850 021).

Received February 19, 1987.