Regulation of hepatic glucose production during exercise in humans: role of sympathoadrenergic activity

Abstract

To investigate the role of sympathoadrenergic activity on glucose production (Ra) during exercise, eight healthy males bicycled 20 min at 41 +/- 2 and 74 +/- 4% maximal O2 uptake (VO2max; mean +/- SE) either without (control; Co) or with blockade of sympathetic nerve activity to liver and adrenal medulla by local anesthesia of the celiac ganglion (Bl). Epinephrine (Epi) was in some experiments infused during blockade to match (normal Epi) or exceed (high Epi) Epi levels during Co. A constant infusion of somatostatin and glucagon was given before and during exercise. At rest, insulin was infused at a rate maintaining euglycemia. During intense exercise, insulin infusion was halved to mimic physiological conditions. During exercise, Ra increased in Co from 14.4 +/- 1.0 to 27.8 +/- 3.0 mumol.min-1.kg-1 (41% VO2max) and to 42.3 +/- 5.2 (74% VO2max; P < 0.05). At 41% VO2max, plasma glucose decreased, whereas it increased during 74% VO2max. Ra was not influenced by Bl. In high Epi, Ra rose more markedly compared with control (P < 0.05), and plasma glucose did not fall during mild exercise and increased more during intense exercise (P < 0.05). Free fatty acid and glycerol concentrations were always lower during exercise with than without celiac blockade. We conclude that high physiological concentrations of Epi can enhance Ra in exercising humans, but normally Epi is not a major stimulus. The study suggests that neither sympathetic liver nerve activity is a major stimulus for Ra during exercise. The Ra response is enhanced by a decrease in insulin and probably by unknown stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Four grams of glucose

“…By combining isotopes and hepatic arterial-venous differences, glucagon was shown to be key to both the glycogenolytic and gluconeogenic responses to exercise (99). Studies (41,49,54,103) conducted in human subjects were consistent with those findings.…”

Activation of the mitogen-activated protein kinase (MAPK) signalling pathway in the liver of mice is related to plasma glucose levels after acute exercise

“…However, strategies designed to specifically address the function of hepatic adrenergic stimulation during exercise, e.g. hepatic adrenoreceptor blockade in dogs [40], or inhibition of hepatic innervation in humans [41], do not support an important role in the stimulation of hepatic glucose output. Of course, this does not exclude the possibility that catecholamines are involved in the activation of hepatic MAPK signalling during exercise.…”

Metabolic and endocrine response to exercise: sympathoadrenal integration with skeletal muscle

“…The exercise-induced increase in catecholamine concentration is of sufficient magnitude to stimulate glycogenolysis in both the liver (Kjaer et al 1993, Kreisman et al 2003 and skeletal muscle (Richter et al 1981, Spriet et al 1988. Under resting conditions, Chasiotis et al (1983) demonstrated that infusing epinephrine resulted in an increase in skeletal muscle phosphorylase a and decrease in glycogen synthase I activity with a modest but significant decrease in glycogen content.…”

“…However, they also noted that during exercise with the adrenaline infusion, the metabolic clearance rate of glucose was lowered, which would also have an effect of elevating plasma glucose. Kjaer et al (1993) examined the effects of blockade of the sympathetic nerves innervating the liver and adrenal medulla on the metabolic response to lowand moderate-intensity exercise. Blockade of celiac ganglion resulted in a 50% reduction in plasma epinephrine when compared with the control (no blockade) condition; however, the plasma concentration of norepinephrine was not affected by celiac blockade.…”