TY - JOUR
T1 - The effect of diabetes on expression of β1-, β2-, and β3-adrenoreceptors in rat hearts
AU - Dinçer, Ü Deniz
AU - Bidasee, Keshore R.
AU - Güner, Şahika
AU - Tay, Ayin
AU - Özçelikay, A. Tanju
AU - Altan, V. Melih
PY - 2001
Y1 - 2001
N2 - Diabetic hearts exhibit decreased responsiveness to stimulation by β-adrenoreceptor (β-AR) agonists. This decrease in activity may be due to changes in expression and/or signaling of β-AR. Recently we showed that right atrial strips from 14-week streptozotocin (STZ)-induced diabetic rat hearts exhibit decreased responsiveness to β1-AR agonist stimulation, but not to β2-AR agonist. In the present study, we investigated the effects of long-term diabetes on the expression of cardiac β1-, β2-, and β3-ARs and looked at whether these changes could be restored with insulin treatment. Using reverse transcription-polymerase chain reaction (RT-PCR), PAGE, and Western blot analysis, we found that β1-AR mRNA and protein levels decreased by 34.9 ± 5.8 and 44.4 ± 5.8%, respectively, in 14 week-STZ-treated diabetic rat hearts when compared with age-matched controls. On the other hand, mRNA levels encoding β2- and β3-ARs increased by 72.5 ± 16.6 and 97.3 ± 26.1%, respectively. Although the latter translated into a proportional increase in β3-AR protein levels (100.0 ± 17.0%), β2-AR protein levels decreased to 82.6 ± 1.1% of control. Insulin treatment for 2 weeks, after 12 weeks of untreated diabetes, partially restored β1-AR mRNA and protein levels to 60.1 ± 8.4 and 83.2 ± 5.0%, respectively, of control. Although insulin treatment minimally attenuated the rise in mRNA levels encoding β2- and β3-ARs, the steady-state levels of these proteins returned to near control values. These data suggest that the decreased responsiveness of diabetic hearts to stimulation of β-AR agonists may be due to a decrease in β1-AR and an increase β3-AR expression.
AB - Diabetic hearts exhibit decreased responsiveness to stimulation by β-adrenoreceptor (β-AR) agonists. This decrease in activity may be due to changes in expression and/or signaling of β-AR. Recently we showed that right atrial strips from 14-week streptozotocin (STZ)-induced diabetic rat hearts exhibit decreased responsiveness to β1-AR agonist stimulation, but not to β2-AR agonist. In the present study, we investigated the effects of long-term diabetes on the expression of cardiac β1-, β2-, and β3-ARs and looked at whether these changes could be restored with insulin treatment. Using reverse transcription-polymerase chain reaction (RT-PCR), PAGE, and Western blot analysis, we found that β1-AR mRNA and protein levels decreased by 34.9 ± 5.8 and 44.4 ± 5.8%, respectively, in 14 week-STZ-treated diabetic rat hearts when compared with age-matched controls. On the other hand, mRNA levels encoding β2- and β3-ARs increased by 72.5 ± 16.6 and 97.3 ± 26.1%, respectively. Although the latter translated into a proportional increase in β3-AR protein levels (100.0 ± 17.0%), β2-AR protein levels decreased to 82.6 ± 1.1% of control. Insulin treatment for 2 weeks, after 12 weeks of untreated diabetes, partially restored β1-AR mRNA and protein levels to 60.1 ± 8.4 and 83.2 ± 5.0%, respectively, of control. Although insulin treatment minimally attenuated the rise in mRNA levels encoding β2- and β3-ARs, the steady-state levels of these proteins returned to near control values. These data suggest that the decreased responsiveness of diabetic hearts to stimulation of β-AR agonists may be due to a decrease in β1-AR and an increase β3-AR expression.
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U2 - 10.2337/diabetes.50.2.455
DO - 10.2337/diabetes.50.2.455
M3 - Article
C2 - 11272160
AN - SCOPUS:0035140242
SN - 0012-1797
VL - 50
SP - 455
EP - 461
JO - Diabetes
JF - Diabetes
IS - 2
ER -