AIM: Adrenaline has widespread metabolic actions, including stimulation of lipolysis and induction of insulin resistance and hyperlactatemia. Systemic adrenaline administration, however, generates a very complex hormonal and metabolic scenario. No studies employing regional, placebo controlled and adrenaline infusion exist. Our study was designed to test the hypothesis that local placebo controlled leg perfusion with adrenaline directly increases local lactate release, stimulates lipolysis, induces insulin resistance and leaves protein metabolism unaffected. METHODS: We studied seven healthy volunteers with bilateral femoral vein and artery catheters during 3-h basal and 3-h hyperinsulinemic (0.6 mU kg(-1) min(-1) ) euglycemic clamp conditions. One femoral artery was perfused with saline and the other with adrenaline (0.4 μg min m(-2) ). Lipid metabolism was quantified with [9,10-(3) H] palmitate and amino acid metabolism with (15) N-phenylalanine and lactate and glucose by raw arterio-venous differences. RESULTS:Femoral vein plasma adrenaline increased ≈eightfold in the perfused leg with unaltered blood flows. Adrenaline perfusion significantly increased local leg lactate release from 0.01 to 0.25 mmol min(-1) per leg, palmitate release in the basal state 11.5-16.9 μmol min(-1) per leg and during the clamp 2.62-8.44 μmol min(-1) per leg. Glucose uptake decreased during the clamp from ≈180 to 30 μmol min(-1) per leg. Phenylalanine kinetics was not affected by adrenaline. CONCLUSION:Adrenaline directly increases lactate release and lipolysis and inhibits insulin-stimulated glucose uptake in the perfused human leg. Adrenaline has no direct effects on peripheral amino acid metabolism. Adrenaline-induced lactate release from striated muscle may be an important mechanism underlying hyperlactatemia in the critically ill.
RCT Entities:
AIM: Adrenaline has widespread metabolic actions, including stimulation of lipolysis and induction of insulin resistance and hyperlactatemia. Systemic adrenaline administration, however, generates a very complex hormonal and metabolic scenario. No studies employing regional, placebo controlled and adrenaline infusion exist. Our study was designed to test the hypothesis that local placebo controlled leg perfusion with adrenaline directly increases local lactate release, stimulates lipolysis, induces insulin resistance and leaves protein metabolism unaffected. METHODS: We studied seven healthy volunteers with bilateral femoral vein and artery catheters during 3-h basal and 3-h hyperinsulinemic (0.6 mU kg(-1) min(-1) ) euglycemic clamp conditions. One femoral artery was perfused with saline and the other with adrenaline (0.4 μg min m(-2) ). Lipid metabolism was quantified with [9,10-(3) H] palmitate and amino acid metabolism with (15) N-phenylalanine and lactate and glucose by raw arterio-venous differences. RESULTS: Femoral vein plasma adrenaline increased ≈eightfold in the perfused leg with unaltered blood flows. Adrenaline perfusion significantly increased local leg lactate release from 0.01 to 0.25 mmol min(-1) per leg, palmitate release in the basal state 11.5-16.9 μmol min(-1) per leg and during the clamp 2.62-8.44 μmol min(-1) per leg. Glucose uptake decreased during the clamp from ≈180 to 30 μmol min(-1) per leg. Phenylalanine kinetics was not affected by adrenaline. CONCLUSION:Adrenaline directly increases lactate release and lipolysis and inhibits insulin-stimulated glucose uptake in the perfused human leg. Adrenaline has no direct effects on peripheral amino acid metabolism. Adrenaline-induced lactate release from striated muscle may be an important mechanism underlying hyperlactatemia in the critically ill.
Authors: Ermina Bach; Roni R Nielsen; Mikkel H Vendelbo; Andreas B Møller; Niels Jessen; Mads Buhl; Thomas K-Hafstrøm; Lars Holm; Steen B Pedersen; Henriette Pilegaard; Rasmus S Biensø; Jens O L Jørgensen; Niels Møller Journal: Diabetes Date: 2013-07-08 Impact factor: 9.461