TY - JOUR

T1 - β2-agonist induces net leg glucose uptake and free fatty acid release at rest but not during exercise in young men

AU - Onslev, Johan Dejgaard

AU - Jensen, Jørgen

AU - Bangsbo, Jens

AU - Wojtaszewski, Jørgen

AU - Hostrup, Morten

N1 - CURIS 2019 NEXS 029

PY - 2019

Y1 - 2019

N2 - Objective: The role of selective β2-adrenergic stimulation in regulation of leg glucose uptake and free fatty acid (FFA) balance is inadequately explored in humans. The objective of this study was to investigate β2-adrenergic effects on net leg glucose uptake and clearance, as well as FFA balance at rest and during exercise.Design: The study was a randomized, placebo-controlled crossover trial, where 10 healthy men received either infusion of β2-agonist terbutaline (0.2 to 0.4 mg) or placebo. Net leg glucose uptake and clearance, and FFA balance were determined at rest and during 8 min of knee extensor exercise using Fick's principle. Vastus lateralis muscle biopsies were collected at rest and at cessation of exercise. The primary outcome measure was net leg glucose uptake.Results: At rest, net leg glucose uptake and clearance were 0.35 (±0.16) mmol/min and 41 (±17) mL/min (mean ± 95% CI) higher (P < 0.001) for terbutaline than placebo, corresponding to increases of 84% and 70%. During exercise, no treatment differences were observed in net leg glucose uptake, whereas clearance was 101 (±86) mL/min lower (P < 0.05) for terbutaline than placebo. At rest, terbutaline induced a net leg FFA release of 21 (±14) µmol/min, being different from placebo (P = 0.04). During exercise, net leg FFA uptake was not different between the treatments.Conclusions: These observations indicate that β2-agonist alters net leg glucose uptake and clearance, as well as FFA balance in humans, which is associated with myocellular β2-adrenergic and insulin-dependent signaling. Furthermore, the study shows that exercise confounds the β2-adrenergic effect on net leg glucose uptake and FFA balance.

AB - Objective: The role of selective β2-adrenergic stimulation in regulation of leg glucose uptake and free fatty acid (FFA) balance is inadequately explored in humans. The objective of this study was to investigate β2-adrenergic effects on net leg glucose uptake and clearance, as well as FFA balance at rest and during exercise.Design: The study was a randomized, placebo-controlled crossover trial, where 10 healthy men received either infusion of β2-agonist terbutaline (0.2 to 0.4 mg) or placebo. Net leg glucose uptake and clearance, and FFA balance were determined at rest and during 8 min of knee extensor exercise using Fick's principle. Vastus lateralis muscle biopsies were collected at rest and at cessation of exercise. The primary outcome measure was net leg glucose uptake.Results: At rest, net leg glucose uptake and clearance were 0.35 (±0.16) mmol/min and 41 (±17) mL/min (mean ± 95% CI) higher (P < 0.001) for terbutaline than placebo, corresponding to increases of 84% and 70%. During exercise, no treatment differences were observed in net leg glucose uptake, whereas clearance was 101 (±86) mL/min lower (P < 0.05) for terbutaline than placebo. At rest, terbutaline induced a net leg FFA release of 21 (±14) µmol/min, being different from placebo (P = 0.04). During exercise, net leg FFA uptake was not different between the treatments.Conclusions: These observations indicate that β2-agonist alters net leg glucose uptake and clearance, as well as FFA balance in humans, which is associated with myocellular β2-adrenergic and insulin-dependent signaling. Furthermore, the study shows that exercise confounds the β2-adrenergic effect on net leg glucose uptake and FFA balance.

U2 - 10.1210/jc.2018-01349

DO - 10.1210/jc.2018-01349

M3 - Journal article

C2 - 30285125

VL - 104

SP - 647

EP - 657

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 3

ER -