EFFECT OF PHYSIOLOGICAL CONCENTRATIONS OF INSULIN AND GLUCAGON ON THE RELATIONSHIP BETWEEN NONESTERIFIED FATTY-ACIDS AVAILABILITY AND KETONE-BODY PRODUCTION IN HUMANS

To determine the effect of insulin and glucagon on the transformation of nonesterified fatty acids (NEFA) into ketone bodies (KB), we measured simultaneously in normal subjects NEFA and KB kinetics at different NEFA levels in the presence of basal (control test) or increasing insulin concentrations with glucagopenia (somatostatin + insulin infusion, insulin test) and without glucagopenia (somatostatin + insulin + glucagon infusion, glucagon test). NEFA levels were controlled during these tests by an intravenous (IV) infusion of a triglyceride emulsion. During the control test, a moderate increase of NEFA (464 ± 30 to 715 ± 56 μmol/L) increased the percentage of NEFA converted into KB (13.3% ± 1.4% to 26.4% ± 2.1%, P < .05), and there was a linear relationship between this percentage and NEFA levels (r = .788, P < .01). During the insulin and glucagon tests, the progressive increase in NEFA induced by the triglyceride emulsion infusion was associated, despite the increase of insulinemia, with an increase in KB production rate (P < .05) and in the proportion of NEFA used for ketogenesis in the presence (8.1% ± 1.2% to 14.2% ± 6.3%, P < .05) and absence (15.7% ± 2.8% to 25.2% ± 3.99%, P < 0.05) of glucagopenia. In both tests, this percentage was always linearly related with NEFA levels (P < .05) and the slopes of these relationships were comparable to that observed in the control test. However, the fraction of NEFA used for ketogenesis was always higher (P < .05) during glucagon substitution than in its absence. Last, the study of type 1 diabetic patients with various degrees of metabolic control showed that this percentage of NEFA used for ketogenesis was rather related to increasing NEFA level (P < .05) than to decreasing insulin concentration (P>10). In conclusion, within the range of NEFA and insulin attained in this study, we did not obtain evidence for a direct hepatic antiketogenic action of insulin, whereas glucagon appears to stimulate ketogenesis at physiological concentrations. © 1991.