Key points are not available for this paper at this time.
BACKGROUND: The aim was to investigate the ability of insulin to modulate the response to beta-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 muU/mL. Dose-response curves for isoproterenol on insulin background were also assessed in the presence and absence of a selective antagonist for beta(2)-adrenoceptor, ICI, at the dose of 5 x 10(-8) mol/L. RESULTS: Insulin did not modify the dose-response curve to calcium (EC(50): 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 EC(50) of isoproterenol (EC(50): 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 EC(50) value of isoproterenol, but insulin was still able to shift to the left dose-response curve of isoproterenol and to reduce significantly the EC(50) of isoproterenol also in the presence of ICI (EC(50): 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 beta(1)-adrenoceptors without effects on beta-adrenoceptor independent adenylate cyclase-related pathway.
Ferrara et al. (Tue,) studied this question.