Diabetes-induced down-regulation of beta(1)-adrenoceptor mRNA expression in rat heart

The present study addressed the question of whether the number of myocardia l beta-adrenoceptors in rats with 4- to 6-week streptozotocin-induced diabe tes is regulated in a transcriptional or translational manner. Radioligand binding experiments with [H-3]CGP 12177 {4-(3-t-butylamino-2-hydroxypropoxy )-[5,7-H-3]benzimidazol-2-one} showed that the density of beta-adrenoceptor s fell by 50% with no change in affinity in diabetic rat ventricular myocar dium compared with age-matched control myocardium. The relative content of beta(1)-adrenoceptor mRNA in diabetic myocardium also was reduced from the control level by 57%, as determined by northern blot analysis. The reductio ns in myocardial beta-adrenoceptor number and beta(1)-adrenoceptor mRNA obs erved in diabetes were prevented by insulin therapy. These data indicate th at the diminished density of myocardial beta-adrenoceptors in diabetes occu rred, at least in part, at the mRNA level. (C) 1999 Elsevier Science Inc.