, Volume 13, Issue 2, pp 305–317 | Cite as

Insulin inhibits β-adrenergic action in ischemic/reperfused heart: a novel mechanism of insulin in cardioprotection

Original Paper



Sympathetic overactivity is closely connected with cell injury and contractile dysfunction during myocardial ischemia/reperfusion (MI/R). Insulin exerts protection for the I/R heart and the underlying mechanisms remain unclear. This study aimed to investigate the ability of insulin to modulate β-adrenergic actions on myocardial contraction and post-ischemic injury in acute MI/R and the underlying mechanism.


Isolated hearts from adult SD rats were subjected to MI/R (30 min/2 h) and treated with isoproterenol (ISO) or/and insulin. Myocardial contraction, cardiomyocyte apoptosis, myocardial injury and infarction were assessed. In a separate study, isolated ventricular myocytes were subjected to simulated I/R (15/30 min) and myocyte shortening and intracellular Ca2+ transient in response to ISO during reperfusion were assessed with presence or absence of insulin.


In isolated I/R hearts, insulin largely reversed the ISO-associated contractile functional impairment at 2 h after MI/R, inhibiting ISO-induced declines in heart rate and left ventricular systolic pressure by 34.0% and 23.0% and preventing ISO-induced elevation in left ventricular end-diastolic pressure by 28.7% respectively (all < 0.05). In addition, ISO alone resulted in enlarged infarct size, elevated CK and LDH activity and increased apoptotic index in I/R hearts compared with vehicle, which were inhibited by treatment of insulin (all < 0.05). Interestingly, in SI/R cardiomyocytes, insulin alone at 10−7 mol/l increased cell contraction whereas attenuated the positive inotropic response to ISO (10−9 mol/l) during R as evidenced by a 18.7% reduction in peak twitch amplitude and a 23.9% reduction in calcium transient amplitude (both < 0.05). Moreover, insulin blunted ISO-mediated increase in PKA activity, enhanced the PKA-dependent phosphorylation of phospholamban (PLB), resulting in increased sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity.


Insulin attenuated the contractile response to β-AR stimulation and suppressed ISO-elicited cardiac dysfunction and cell injury in MI/R. The inhibitory effect of insulin on the β-adrenergic action involved the inhibition of PKA-mediated Ca2+ transient and promotion of post-ischemic Ca2+ handling.


β-Adrenoceptor Insulin Ischemia and reperfusion injury Apoptosis PKA 


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Departments of Cardiology and Physiology, Xijing HospitalFourth Military Medical UniversityXi’anChina
  2. 2.Department of Cardiology, Xijing HospitalFourth Military Medical UniversityXi’anChina
  3. 3.Department of PhysiologyFourth Military Medical UniversityXi’anChina

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