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Effects of Ketone Bodies on Basal and Insulin-Stimulated Glucose Utilization in Man^*

INSERM U.197 Facult' de Médecine Alexix Carrel 69008 Lyon Service d’Endocrinologie et desMaladiesdela Nutrition, Hôspital de l’Antiquaille 69005 Lyon
Service de Radioanalyse M'decine Nucl'aire Hôspital Cardio-Vasculaire (R.C.) 69500Bron France

Address requests forreprints toDr.M.Beylot, Faculte de Medecine Alexis Carrel, INSERM U.197, rue Guillaume Paradin, Lyon Cedex 08, F–69372 France.

Using the euglycemic clamp technique, we in vestigated the effects of high ketone body levels on basaland insulinstimulated glucose utilization in normal subjects. Infusionof sodium acetoacetate in the postabsorptive state raised ketone body levels from 150±(150±E) junol/liter tomore than 1 mmol/liter. Endogenous glucose production declined from2.71 150±0.20mg kg^-1 min^-1 to 1.75 + 0.26(P< 0.01) and glucose utilization from 2.71150±0.20to 1.98 150±0.17 mg kg^-1 min^-1(P <0.01), while blood glucose was maintained at the initial levelby the infusion of glucose. There were no changes inplasmaglucagon, insulin, orC–peptide. Plasma nonesterified fatty acids (P< 0.01) andblood glycerol (P < 0.01) andalanine (P< 0.05) decreased, while blood lactate increased (P<0.01). Infusion of sodium bicarbonate hadno effect on glucose kinetics. The de creases inglucose utilization andendogenous glucose production during the infusion of acetoacetate were notmodified when the fall of plasma nonesterified fatty acids was prevented byiv heparin injection. During control euglycemichyperinsulinemic clamps (1 and10 mU kg^-1 min^-1insulin infusion), endogenous glucose production wassuppressed atthe lowest insulin infusion rate; glucose utilization increased first to 7.32 150±0.96mg kg^-1 min^-1 and then to 16.5150±1.27 mg kg^-1 min^-1. During euglycemic hyperinsulinemic clamps with simultaneous sodium acetoacetate infusion, similar insulinlevels were attained; endogenous glucose production was also suppressed at the lowest insulin infusion rate, andinsulin-stimulated glucose utilization rates (7.93 150±1.70 and 15.80150±1.30mg kg^-1 min^-1 were notmodified.In conclusion, acetoacetate infusion decreased basal, but not insulin-stimulated, glucose utilization. Theincrease in lactate during acetoacetate infusion in thepostabsorptive state suggests that ketone body acted by decreasing pyruvate oxidation.

^* This work was supported by a grant from the Etablissement Public Regional (Rhone–Alpes) and the Hospices Civils de Lyon for the Artificial Pancreas.

Received October 23, 1985.

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