Decreased expression of beta1- and beta2-adrenoceptors in human diabetic atrial appendage

Abstract

Background: Using the streptozotocin-induced diabetic rat model, we have recently showed that the expression and function of beta1-adrenoreceptor were decreased in the diabetic rat heart. However, the effect of diabetes on expression of beta-adrenoreceptors in human cardiac tissue remains undefined. Therefore, the focus of the present study was to investigate the effect of diabetes on mRNA encoding beta1- and beta2-ARs in human atrial tissues.

Methods: Right atrial appendages from five diabetic (mean age 65 +/- 4.5; 4 female, 1 male) and five nondiabetic patients (mean age 56.2 +/- 2.8; 4 male, 1 female) undergoing coronary artery bypass grafting were collected and assayed using reverse transcriptase-polymerase chain reaction (RT-PCR) for their mRNA content. No patient from these two groups suffered from acute myocardial infarction and/or failure. All diabetic patients received insulin for at least two years and had been diagnosed as diabetics for at least five years.

Results: When compared with levels in nondiabetics, steady state levels of mRNA encoding beta1-adrenoreceptor decreased by 69.2 +/- 7.6% in diabetic patients while beta2-adrenoreceptor mRNA decreased by 32.2 +/- 5.5% (p < 0.001).

Conclusions: Our findings show a decreased expression of beta1- and beta2-adrenoreceptors in human diabetic atrial appendage.

Figure 1

Patients undergoing coronary arterial by-pass grafting during a two month period at Baskent University, Ankara, Turkey. (A) mean age of patients (B) Percentage distribution of patients according to gender and diabetic state.

Figure 2

Reverse transcription-polymerase chain reaction (RT-PCR) products obtained from diabetic (5) and nondiabetic (5) human atrial appendages. Total RNA was reverse-transcribed using oligo dT_12–18 and the first strand cDNA was subjected to amplification by PCR. The samples were loaded onto 2% agarose gel and electrophoresed for 2 hr at 100 V. A. Example and quantitation of signals for β₁-AR obtained using RT-PCR reactions. B. Example and quantitation of signals for β₂-AR obtained using RT-PCR reactions. C. Example and quantitation of signals for β-actin obtained using RT-PCR reactions. Values shown are mean ± SEM obtained from five experiments. *P < vs. control group.

Figure 3

β₁/β₂ mRNA ratio in diabetic and non-diabetic human atrial appendages.