title: Fatty acid-independent inhibition of hepatic ketone body production by insulin in humans.
abstract: 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.
authors.affiliation: Department of Medicine, University Hospital, Basel, Switzerland.
authors.forename: U
authors.initials: U
authors.lastname: Keller
authors.forename: P P
authors.initials: PP
authors.lastname: Gerber
authors.forename: W
authors.initials: W
authors.lastname: Stauffacher
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D005934:Glucagon / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood*; D007657:Ketone Bodies / Q000096:biosynthesis*; D007700:Kinetics; D007773:Lactates / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007657:Ketone Bodies; D007773:Lactates; D005934:Glucagon