Diabetes-induced down-regulation of beta1-adrenoceptor mRNA expression in rat heart

The present study addressed the question of whether the number of myocardial beta-adrenoceptors in rats with 4- to 6-week streptozotocin-induced diabetes is regulated in a transcriptional or translational manner. Radioligand binding experiments with [3H]CGP 12177 {4-(3-t-butylamino-2-hydroxypropoxy)-[5,7-3H]benzimidazol-2-one} showed that the density of beta-adrenoceptors fell by 50% with no change in affinity in diabetic rat ventricular myocardium compared with age-matched control myocardium. The relative content of beta1-adrenoceptor mRNA in diabetic myocardium also was reduced from the control level by 57%, as determined by northern blot analysis. The reductions in myocardial beta-adrenoceptor number and beta1-adrenoceptor mRNA observed in diabetes were prevented by insulin therapy. These data indicate that the diminished density of myocardial beta-adrenoceptors in diabetes occurred, at least in part, at the mRNA level.