Suppression of Glucose Production and Stimulation of Insulin Secretion by Physiological Concentrations of Ketone Bodies in Man

Abstract

To determine the mechanism by which ketonebodies decrease plasma glucose in man, seven normal postabsorptivevolunteers were infused for 3 h with β-hydroxybutyrate.Total plasma ketone bodies (β-hiydroxybutyrate plus acetoacetate)increased to levels (∼2.5 mM) observed after a 2- to 3-dayfast in normal subjects. Plasma glucose decreased 10% concomitantwith decreases of 25% and 10%, respectively, in the rates ofglucose production and glucose utilization determined isotopicallywith [3–³H]glucose. Plasma insulin and glucagon concentrationswere unaltered, but plasma C-peptide levels increased from2.6 ± 0.1 ng/ml to a maximum of 3.9 ± 0.2 ng/ml at 30 min (P < 0.01) and remained significantly increased for more than 2 h.Plasma alanine decreased approximately 14% (P < 0.05), whileplasma lactate increased 25% (P < 0.01) so that there was no netdecrease in the combined levels of these gluconeogenic substrates.These results demonstrate that physiological incrementsin circulating ketone body concentrations decrease plasma glucosein normal man by suppressing glucose production, an effectwhich can be explained by the stimulation of insulin secretionbeing reflected only in changes in plasma C-peptide. Thus,changes in pancreatic B cell function not sufficient to alterperipheral plasma insulin levels may cause significant changesin hepatic glucose production. (JClin Endocrinol Metab52: 34,1981)