The action of ?-adrenergic blocking and stimulating agents on insulin secretion. Characterization of the type of ? receptor

1 The effect of oral doses of the pl-selective adrenoceptor antagonist atenolol (50 mg), the non-selective antagonist propranolol (40 mg) and placebo was investigated during exercise in a crossover comparison in six healthy but untrained subjects. Descriptors of ventilation, respiratory gas exchange, and arterialized blood lactate and glucose were obtained during steady state bicycle ergometric exercise at 20% and 60% of the subjects' previously determined maximal oxygen uptake (Vo2 max). 2 At these work intensities, the previously reported increase of respiratory exchange ratio (RER) during non-selective 3-adrenoceptor blockade was found to be trivial (placebo = 0.96 ± 0.03 s.e. mean; propranolol = 0.97 + 0.01; atenolol = 0.97 + 0.04; 60% Vo2 max, 10 min exercise) and only present during the early minutes of effort.Oxygen uptake and carbon dioxide production did not differ between treatments. 3 Both drugs produced highly significant falls in peak expiratory flow (PEF) rates and tidal volume (VT) which were compensated by an increase in respiratory rate. PEF, 60% Vo2 max: placebo = 3.8 + 0.3 l/s; propranolol 3.6 + 0.3 1/s (P < 0.03); atenolol 3.1 + 0.3 1/s (P < 0.01). VT, 60% Vo2 max: placebo 2.0 + 0.1 1; propranolol 1.8 + 0.2 1 (P < 0.05); atenolol 1.7 ± 0.1 1 (P < 0.01). 4 Arterialized lactate was significantly elevated during work at 20% and 60% Vo2 max, but rose progressively at the 60% Vo2 max load. Ventilation, oxygen uptake and ventilatory equivalent for carbon dioxide also rose progressively at this workload. Ventilatory equivalent for oxygen showed no significant rise. There were no treatment differences, either at the aerobic or anaerobic workloads. During steady state exercise, previously described determinants of anaerobic threshold (RER, 02 ventilatory equivalent) appear not to be valid. 5 We conclude that normoglycaemic aerobic or anaerobic work is associated with a I3l-adrenoceptor response which reduces airway resistance. Despite antagonism of lipolysis and hepatic glycogenolysis, ,B-adrenoceptor blockade does not appear to alter the pattern of substrate utilization.

Section: Discussionmentioning

confidence: 99%

Beta 1‐selective and non‐selective beta‐adrenoceptor blockade, anaerobic threshold and respiratory gas exchange during exercise.

McLeod¹,

Knopes²,

Shand³

et al. 1985

“…Blockade of pancreatic fi-adrenoceptors mediating insulin release Loubatieres, Mariani, Sorel & Savi (1971) suggested that the,-adrenoceptors in the pancreas mediating insulin release are of the f2-type.…”

Section: Plasma Renin Activitymentioning

confidence: 99%

Blockade of isoprenaline‐induced changes in plasma free fatty acids, immunoreactive insulin levels and plasma renin activity in healthy human subjects, by propranolol, pindolol, practolol, atenolol, metoprolol and acebutolol.

Harms¹,

Gooren²,

Spoelstra³

et al. 1978

I The effects of intravenously administered propranolol 0.01 and 0.03, pindolol 0.001 and 0.003, practolol 0.12 and 0.36, atenolol 0.03 and 0.09, metoprolol 0.045 and 0.135 and acebutolol 0.12 and 0.36 mg/kg, on isoprenaline-induced changes in heart rate, blood pressure, plasma free fatty acids, immunoreactive insulin plasma levels and plasma renin activity were determined in six healthy human subjects. 2 Propranolol, atenolol and metoprolol had a stronger effect on resting heart rate than practolol, acebutolol and pindolol, probably reflecting differences in intrinsic f,-sympathomimetic activity.Antagonist potencies against isoprenaline-induced changes in heart rate and blood pressure suggested cardioselectivity for practolol, atenolol, metoprolol and the lower dose of acebutolol and noncardioselectivity for propranolol, pindolol and the higher dose of acebutolol. 3 All six f-adrenoceptor blocking agents were able, to a varying extent, to antagonize the isoprenaline-induced increases in plasma free fatty acids and plasma immunoreactive insulin levels. In general, the cardioselective agents were relatively less effective antagonists than the non-cardioselective agents.4 Resting plasma renin activity was reduced by all six fJ-adrenoceptor blocking agents, suggestive of the presence of fJ1-adrenoceptors mediating renin release, but the non-cardioselective agents propranolol and pindolol seemed relatively more effective in antagonizing isoprenaline-induced increases in plasma renin activity than the cardioselective agents, which indicates that 62-adrenoceptors might also be involved.5 The results are compatible with the hypothesis that both #,-and fJ2-adrenoceptors are involved in the regulation oflipolysis, insulin release and renin release.

“…Alternatively it may be secondary to an increase in insulin levels (Phillips et al, 1980;William-Olsson et al, 1979). Such a rise in insulin levels is seen in dogs following an infusion of salbutamol, a 832-adrenoceptor agonist (Loubatieres et al, 1971). This is not blocked by the ,1i specific blocker practolol whereas it is by the non-selective /3-adrenoceptor blocker propranolol.…”

Section: Discussionmentioning

confidence: 99%

Can the biochemical responses to a beta 2‐adrenoceptor stimulant be used to assess the selectivity of beta‐adrenoceptor blockers?

Smith¹,

Kendall²,

Worthington³

et al. 1983

The extent to which f8-adrenoceptor blocking drugs counteract the biochemical responses to an infusion of terbutaline, a f82-adrenoceptor agonist, has been investigated. In this study the 3,0-selectivity of metoprolol was compared with the non-selective ,3-adrenoceptor blocker propranolol. The hypokalaemia produced by an infusion of terbutaline was reduced by low dose (50 mg) and high dose (200 mg) metoprolol and by low dose (40 mg) and high dose (160 mg) propranolol. The effects of propranolol on terbutaline induced hypokalaemia were more marked than those of metoprolol at both low dose (P = 0.01) and high dose (P = 0.05). Furthermore low dose metoprolol had less effect than high dose metoprolol (P = 0.05). The serum potassium appeared to rise slightly after propranolol. Low and high doses of both ,8-adrenoceptor blockers markedly reduced the terbutalineinduced hyperglycaemia, but the differences between the two drugs were not statistically significant.