Abstract
Cerebral non-oxidative carbohydrate consumption may be driven by a β2-adrenergic mechanism. This study tested whether the 46G > A (G16R) single nucleotide polymorphism of the β2-adrenergic receptor gene (ADRB2) influences the metabolic and cerebrovascular responses to administration of adrenaline. Forty healthy Caucasian men were included from a group of genotyped individuals. Cardio- and cerebrovascular variables at baseline and during a 60-min adrenaline infusion (0.06 μg kg−1 min−1) were measured by Model flow, near-infrared spectroscopy and transcranial Doppler sonography. Blood samples were obtained from an artery and a retrograde catheter in the right internal jugular vein. The ADRB2 G16R variation had no effect on baseline arterial glucose, but during adrenaline infusion plasma glucose was up to 1.2 mM (CI95: 0.36–2.1, P < 0.026) higher in the Gly16 homozygotes compared with Arg16 homozygotes. The extrapolated steady-state levels of plasma glucose was 1.9 mM (CI95: 1.0 –2.9, PNLME < 0.0026) higher in the Gly16 homozygotes compared with Arg16 homozygotes. There was no change in the cerebral oxygen glucose index and the oxygen carbohydrate index during adrenaline infusion and the two indexes were not affected by G16R polymorphism. No difference between genotype groups was found in cardiac output at baseline or during adrenaline infusion. The metabolic response of glucose during adrenergic stimulation with adrenaline is associated to the G16R polymorphism of ADRB2, although without effect on cerebral metabolism. The differences in adrenaline-induced blood glucose increase between genotypes suggest an elevated β2-adrenergic response in the Gly16 homozygotes with increased adrenaline-induced glycolysis compared to Arg16 homozygotes.
Highlights
Cerebral energy metabolism at rest is provided almost exclusively by glucose and the molar ratio between the cerebral uptake of O2 to that of glucose is close to 6 (Quistorff et al, 2008)
The β2-adrenergic receptor gene (ADRB2) G16R variation had no effect on baseline arterial glucose, but during adrenaline infusion plasma glucose was up to 1.2 mM (CI95: 0.36 – 2.1, P < 0.026) higher in the Gly16 homozygotes compared with Arg16 homozygotes
The metabolic response of glucose during adrenergic stimulation with adrenaline is associated to the G16R polymorphism of ADRB2, without effect on cerebral metabolism
Summary
Cerebral energy metabolism at rest is provided almost exclusively by glucose and the molar ratio between the cerebral uptake of O2 to that of glucose (the O2-glucose index; OGI) is close to 6 (Quistorff et al, 2008). The non-synonymous 46 G > A (G16R) single nucleotide polymorphism leading to an amino acid substitution of Gly16Arg segregates with hypertension and asthma (Zaugg and Schaub, 2005; Sayers, 2013) and homozygote Gly subjects demonstrate a larger cardiac output (CO) both at rest and during exercise compared with homozygote Arg subjects (Snyder et al, 2006a; Rokamp et al, 2013). The G16R polymorphism has been associated with insulin resistance (Masuo et al, 2005) and obesity (Daghestani et al, 2012), albeit with inconsistent results (Gjesing et al, 2009) Another polymorphisms in the β2adrenergic receptor gene of functional importance is the 79C > G Q27E and in contrast to the Arg allele, the Glu allele is associated with increased agonist-mediated responsiveness in vasculature (Dishy et al, 2001). The role of haplotypes within ADRB2 is, not known, but Rokamp et al (2013) found no impact of haplotypes on cardiac output
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