Cerebral non-oxidative carbohydrate consumption in humans driven by adrenaline

Abstract

During brain activation, the decrease in the ratio between cerebral oxygen and carbohydrate uptake (6 O(2)/(glucose + (1)/(2) lactate); the oxygen-carbohydrate index, OCI) is attenuated by the non-selective beta-adrenergic receptor antagonist propranolol, whereas OCI remains unaffected by the beta(1)-adrenergic receptor antagonist metroprolol. These observations suggest involvement of a beta(2)-adrenergic mechanism in non-oxidative metabolism for the brain. Therefore, we evaluated the effect of adrenaline (0.08 microg kg(-1) min(-1) i.v. for 15 min) and noradrenaline (0.5, 0.1 and 0.15 microg kg(-1) min(-1) i.v. for 20 min) on the arterial to internal jugular venous concentration differences (a-v diff) of O(2), glucose and lactate in healthy humans. Adrenaline (n = 10) increased the arterial concentrations of O(2), glucose and lactate (P < 0.05) and also increased the a-v diff for glucose from 0.6 +/- 0.1 to 0.8 +/- 0.2 mM (mean +/- s.d.; P < 0.05). The a-v diff for lactate shifted from a net cerebral release to an uptake and OCI was lowered from 5.1 +/- 1.5 to 3.6 +/- 0.4 (P < 0.05) indicating an 8-fold increase in the rate of non-oxidative carbohydrate uptake during adrenaline infusion (P < 0.01). Conversely, noradrenaline (n = 8) did not affect the OCI despite an increase in the a-v diff for glucose (P < 0.05). These results support that non-oxidative carbohydrate consumption for the brain is driven by a beta(2)-adrenergic mechanism, giving neurons an abundant provision of energy when plasma adrenaline increases.

Figure 1. The O₂-to-glucose index (OGI) and the O₂-to-carbohydrate index (OCI) at rest and during adrenaline infusion. Values are means ±s.e.m.

*P < 0.05 compared to baseline (n= 10).

Figure 2. Cummulated uptake rates of O₂, glucose and lactate and the total uptake balance (glucose +¹/₂lactate – 1/6O₂ before, during and after adrenaline infusion

Values are means ±s.e.m. for n= 10. *P < 0.05 compared to baseline, †P < 0.05 compared to infusion.

Figure 3. The O₂-to-glucose index (OGI) and the O₂-to-carbohydrate index (OCI) during saline infusion and during infusion of different doses of noradrenaline (NA)

Low NA (0.5 μg kg⁻¹ min⁻¹), medium NA (1.0 μg kg⁻¹ min⁻¹) and high NA (1.5 μg kg⁻¹ min⁻¹). Values are means ±s.e.m.*P < 0.05 compared to saline infusion (n= 8).