Epinephrine's ketogenic effect in humans is mediated principally by lipolysis.
To quantify epinephrine's effects on acetoacetate and beta-hydroxybutyrate kinetics, we infused subjects with 0.3 and 2.5 micrograms/min epinephrine, either alone or with a concomitant somatostatin infusion with insulin, glucagon, and growth hormone replaced at postabsorptive levels (islet clamp). Additional subjects received no epinephrine but sequential infusions of heparin plus 10% Intralipid at rates of 0.5 and 3.0 ml/min. Both epinephrine and Intralipid increased ketone body appearance (unaffected by islet clamp), augmented the interconversion rates between ketone bodies and, during the 2.5 micrograms/min infusion, caused a marked increase in beta-hydroxybutyrate appearance. The fraction of plasma free fatty acid (FFA) flux appearing as plasma ketones increased from 6 to 7% in the basal state to 11% at the high-epinephrine infusion. This fraction was also unaffected by the islet clamp and was not different from values obtained at similar Intralipid plus heparin-induced elevations in plasma FFA levels. We conclude that epinephrine's ketogenic effect in humans is primarily the result of its lipolytic effect, is accompanied by a significantly increased rate of ketone body interconversion, is manifest largely as an increase in plasma beta-hydroxybutyrate appearance at high plasma epinephrine values, and is not limited by portal insulin at post-absorptive levels.
Avogaro
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A
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63141.
Cryer
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Bier
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DM
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000378:metabolism; D000328:Adult; D004837:Epinephrine / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D006885:Hydroxybutyrates / Q000378:metabolism; D007657:Ketone Bodies / Q000096:biosynthesis* / Q000378:metabolism; D008066:Lipolysis / Q000502:physiology*; D008297:Male; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism
D000090:Acetoacetates; D005227:Fatty Acids; D006885:Hydroxybutyrates; D007657:Ketone Bodies; D010169:Palmitic Acids; D019308:Palmitic Acid; C016635:acetoacetic acid; D020155:3-Hydroxybutyric Acid; D004837:Epinephrine