Insulin-induced changes in β-adrenergic response: An experimental study in the isolated rat papillary muscle

Background The aim was to investigate the ability of insulin to modulate the response to β-adrenergic action on myocardial contractility, assessed as percentage changes of developed tension, in isolated rat papillary muscle. Methods Dose-response curves for isoproterenol, calcium, and forskolin were constructed in an incremental fashion with the presence or absence of insulin at the dose of 50 μU/mL. Dose-response curves for isoproterenol on insulin background were also assessed in the presence and absence of a selective antagonist for β2-adrenoceptor, ICI, at the dose of 5 × 10−8 mol/L. Results Insulin did not modify the dose-response curve to calcium (EC50: 1.4 ± 0.4 mmol/Lfor insulin, n = 8 v 1.5 ± 0.3 mmol/L for control, n = 8; P = not significant), whereas it was able to shift to the left the dose-response curve and reduce significantly the EC50 of isoproterenol (EC50: 0.2 ± 0.2 nmol/L for insulin, n = 13 v 1.1 ± 0.4 nmol/L for control, n = 12; P< .01). ICI shifted to the right dose-response curve of isoproterenol and increased about 10-fold the EC50 value of isoproterenol, but insulin was still able to shift to the left dose-response curve of isoproterenol and to reduce significantly the EC50 of isoproterenol also in the presence of ICI (EC50: 11.0 ± 1.5 nmol/L for ICI, n = 7 v 1.9 ± 0.8 nmol/L for ICI + insulin, n = 7; P< .01). Insulin did not modify the dose-response curve to forskolin. Conclusions Our results suggest that the insulin-induced modulation of contractility is calcium independent and insulin leads to a supersensitization on the β1-adrenoceptors without effects on β-adrenoceptor independent adenylate cyclase-related pathway.