The effect of diabetes on expression of beta1-, beta2-, and beta3-adrenoreceptors in rat hearts.
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.
Dinçer
U D
UD
Department of Pharmacology, Faculty of Pharmacy, University of Ankara, Turkey.
Bidasee
K R
KR
Güner
S
S
Tay
A
A
Ozçelikay
A T
AT
Altan
V M
VM
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values
D007004:Hypoglycemic Agents; D007328:Insulin; D020033:Protein Isoforms; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D012313:RNA