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-ADRENOCEPTORS
1 Department of Pharmacology, DRC Rm 3047, University of Nebraska, Omaha, Nebraska, United States; , United States
2 Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, United States; Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, United States
3 Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, United States
4 Omaha, Nebraska, United States; Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, United States
5 Department of Physiology & Biophysics, University of Nebraska Medical Center, Omaha, Nebraska, United States; Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, United States
6 Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, United States
* To whom correspondence should be addressed. E-mail: kbidasee{at}unmc.edu.
The present study was undertaken to assess cardiac function and characterize 
-adrenoceptor subtypes in hearts of diabetic rats that underwent exercise training (ExT) after the onset of diabetes. Type 1 diabetes was induced in male Sprague-Dawley rats using streptozotocin. Four weeks after induction, rats were randomly divided into two groups. One group was exercised trained for three weeks while the other group remained sedentary. At the end of the protocol, cardiac parameters were assessed using M-Mode echocardiography. A Millar catheter was also used to assess left ventricular hemodynamics with and without isoproterenol stimulation. -adrenoceptors were assessed using Western blots and [3H]dihydroalprenolol binding. After seven weeks of diabetes, heart rate decreased by 21%, fractional shortening by 20%, ejection fraction by 9% and basal and isoproterenol induced dP/dt by 35%. 1- and 2-adrenoceptor proteins were reduced by 60% and 40%, while 3-adrenoceptor protein increased by 125%. Ventricular homogenates from diabetic rats bound 52% less [3H]dihydroalprenolol, consistent with reductions in 1- and 2-adrenoceptors. Three weeks of ExT initiated four weeks after the onset of diabetes minimized cardiac function loss. ExT also blunted loss of 1-adrenoceptor expression. Interestingly, ExT did not prevent diabetes-induced reduction in 2-adrenoceptor or the increased of 3-adrenoceptor expression. ExT also increased [3H]dihydroalprenolol binding, consistent with increased 1-adrenoceptor expression. These findings demonstrate for the first time that ExT initiated after the onset of diabetes blunts primarily 1-adrenoceptor expression loss, providing mechanistic insights for exercise-induced improvements in cardiac function.
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  T. O. Stolen, M. A. Hoydal, O. J. Kemi, D. Catalucci, M. Ceci, E. Aasum, T. Larsen, N. Rolim, G. Condorelli, G. L. Smith, et al. Interval Training Normalizes Cardiomyocyte Function, Diastolic Ca2+ Control, and SR Ca2+ Release Synchronicity in a Mouse Model of Diabetic Cardiomyopathy Circ. Res., September 11, 2009; 105(6): 527 - 536. [Abstract] [Full Text] [PDF]
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