Fatty acid-independent inhibition of hepatic ketone body production by insulin in humans.

To investigate whether elevated plasma insulin or glucagon concentrations are capable of modifying hepatic ketogenesis independently of plasma free fatty acid (FFA) concentrations, ketone body production was determined by [3-14C]acetoacetate infusions in overnight-fasted normal subjects during exogenous supply of FFA (Intralipid and heparin infusion). When plasma FFA concentrations were elevated from 0.73 +/- 0.07 to 1.53 +/- 0.16 mmol/l during low insulin concentrations (approximately equal to 13 microU/ml) in group A (n = 7), total ketone body production increased from 3.6 +/- 0.6 to 8.2 +/- 1.0 mumol.kg-1.min-1 (P less than 0.001). When plasma FFA were similarly elevated during raised plasma insulin concentrations (approximately equal to 110 microU/ml) in group B (n = 5), total ketone body production was only 3.8 +/- 0.8 mumol.kg-1.min-1 (P less than 0.01 vs. group A). Low plasma FFA and low insulin concentrations resulted in total ketone body production of 0.70 +/- 0.18 mumol.kg-1.min-1 in group C (n = 7; P less than 0.01 vs. groups A and B). Elevation of plasma glucagon during Intralipid infusion in group D (n = 7) failed to affect ketogenesis, but the beta-hydroxybutyrate-to-acetoacetate concentration ratio decreased significantly (P less than 0.01). The data indicate that elevation of plasma insulin to high physiological concentrations restrains FFA-induced ketogenesis.