Insulin-induced changes in beta-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 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
Nicola
N
Department of Health Sciences, University of Molise, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Telese/Campoli, Via dei Bagni Vecchi, 82037 Telese Terme, Italy. nferrara@fsm.it
Abete
Pasquale
P
Corbi
Graziamaria
G
Paolisso
Giuseppe
G
Longobardi
Giancarlo
G
Calabrese
Claudio
C
Cacciatore
Francesco
F
Scarpa
Donatella
D
Iaccarino
Guido
G
Trimarco
Bruno
B
Leosco
Dario
D
Rengo
Franco
F
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D007004:Hypoglycemic Agents; D007328:Insulin; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D007545:Isoproterenol; D002118:Calcium