The effect of diabetes on expression of beta1-, beta2-, and beta3-adrenoreceptors in rat hearts.

Abstract:

:Diabetic hearts exhibit decreased responsiveness to stimulation by beta-adrenoreceptor (beta-AR) agonists. This decrease in activity may be due to changes in expression and/or signaling of beta-AR. Recently we showed that right atrial strips from 14-week streptozotocin (STZ)-induced diabetic rat hearts exhibit decreased responsiveness to beta1-AR agonist stimulation, but not to beta2-AR agonist. In the present study, we investigated the effects of long-term diabetes on the expression of cardiac beta1-, beta2-, and beta3-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 beta1-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 beta2- and beta3-ARs increased by 72.5 +/- 16.6 and 97.3 +/- 26.1%, respectively. Although the latter translated into a proportional increase in beta3-AR protein levels (100.0 +/- 17.0%), beta2-AR protein levels decreased to 82.6 +/- 1.1% of control. Insulin treatment for 2 weeks, after 12 weeks of untreated diabetes, partially restored beta1-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 beta2- and beta3-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 beta-AR agonists may be due to a decrease in beta1-AR and an increase beta3-AR expression.

journal_name

Diabetes

journal_title

Diabetes

authors

Dinçer UD,Bidasee KR,Güner S,Tay A,Ozçelikay AT,Altan VM

doi

10.2337/diabetes.50.2.455

subject

Has Abstract

pub_date

2001-02-01 00:00:00

pages

455-61

issue

2

eissn

0012-1797

issn

1939-327X

journal_volume

50

pub_type

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