Skip to main content
Top
Published in: Cardiovascular Diabetology 1/2003

Open Access 01-12-2003 | Original investigation

Decreased expression of β1- and β2-adrenoceptors in human diabetic atrial appendage

Authors: U Deniz Dinçer, Şahika Güner, Aydin Tay, Ebru Arioğlu, Atilay Taşdelen, Sait Aşlamaci, Keshore R Bidasee

Published in: Cardiovascular Diabetology | Issue 1/2003

Login to get access

Abstract

Background

Using the streptozotocin-induced diabetic rat model, we have recently showed that the expression and function of β1-adrenoreceptor were decreased in the diabetic rat heart. However, the effect of diabetes on expression of β-adrenoreceptors in human cardiac tissue remains undefined. Therefore, the focus of the present study was to investigate the effect of diabetes on mRNA encoding β1- and β2-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 β1-adrenoreceptor decreased by 69.2 ± 7.6 % in diabetic patients while β2-adrenoreceptor mRNA decreased by 32.2 ± 5.5 % (p < 0.001).

Conclusions

Our findings show a decreased expression of β1- and β2-adrenoreceptors in human diabetic atrial appendage.
Appendix
Available only for authorised users
Literature
1.
go back to reference Kannel WB, McGee DL: Diabetes and cardiovascular disease: The Framingham Study. JAMA. 1979, 241: 2035-2038. 10.1001/jama.241.19.2035.CrossRefPubMed Kannel WB, McGee DL: Diabetes and cardiovascular disease: The Framingham Study. JAMA. 1979, 241: 2035-2038. 10.1001/jama.241.19.2035.CrossRefPubMed
2.
go back to reference Rodrigues B, McNeill JH: The diabetic heart: metabolic causes for the development of a cardiomyopathy. Cardiovas Res. 1992, 26: 913-922.CrossRef Rodrigues B, McNeill JH: The diabetic heart: metabolic causes for the development of a cardiomyopathy. Cardiovas Res. 1992, 26: 913-922.CrossRef
3.
go back to reference Lefkowitz RJ, Rockman HA, Koch WJ: Catecholamines, cardiac beta-adrenergic receptors, and heart failure. Circulation. 2000, 101: 1634-7.CrossRefPubMed Lefkowitz RJ, Rockman HA, Koch WJ: Catecholamines, cardiac beta-adrenergic receptors, and heart failure. Circulation. 2000, 101: 1634-7.CrossRefPubMed
4.
go back to reference Wang X, Dhalla NS: Modification of beta-adrenoceptor signal transduction pathway by genetic manipulation and heart failure. Mol Cell Biochem. 2000, 214: 131-55. 10.1023/A:1007131925048.CrossRefPubMed Wang X, Dhalla NS: Modification of beta-adrenoceptor signal transduction pathway by genetic manipulation and heart failure. Mol Cell Biochem. 2000, 214: 131-55. 10.1023/A:1007131925048.CrossRefPubMed
5.
go back to reference Fein FS, Aronson RS, Nordin C, Miller-Green B, Sonnenblick EH: Altered myocardial response to ouabain in diabetic rats: mechanics and electro physiology. J Mol Cell Cardiol. 1983, 15: 769-84.CrossRefPubMed Fein FS, Aronson RS, Nordin C, Miller-Green B, Sonnenblick EH: Altered myocardial response to ouabain in diabetic rats: mechanics and electro physiology. J Mol Cell Cardiol. 1983, 15: 769-84.CrossRefPubMed
6.
go back to reference Dinçer ÜD, Bidasee KR, Güner S, Tay A, Özçelikay AT, Altan VM: The effect of diabetes on expression of beta1-, beta2-, and beta3-adrenoreceptors in rat hearts. Diabetes. 2001, 50: 455-61.CrossRefPubMed Dinçer ÜD, Bidasee KR, Güner S, Tay A, Özçelikay AT, Altan VM: The effect of diabetes on expression of beta1-, beta2-, and beta3-adrenoreceptors in rat hearts. Diabetes. 2001, 50: 455-61.CrossRefPubMed
7.
go back to reference Dinçer ÜD, Özçelikay AT, Yýlmaz ED: The effects of chronic L-name and L-arginine administration on beta-adrenergic responsiveness of STZ-diabetic rat atria. Pharmacol Res. 2000, 41: 565-70. 10.1006/phrs.1999.0623.CrossRefPubMed Dinçer ÜD, Özçelikay AT, Yýlmaz ED: The effects of chronic L-name and L-arginine administration on beta-adrenergic responsiveness of STZ-diabetic rat atria. Pharmacol Res. 2000, 41: 565-70. 10.1006/phrs.1999.0623.CrossRefPubMed
8.
go back to reference Dinçer ÜD, Onay A, Arý N, Özçelikay AT, Altan VM: The effects of diabetes on beta-adrenoceptor mediated responsiveness of human and rat atria. Diabetes Res Clin Pract. 1998, 40: 113-22. 10.1016/S0168-8227(98)00034-5.CrossRefPubMed Dinçer ÜD, Onay A, Arý N, Özçelikay AT, Altan VM: The effects of diabetes on beta-adrenoceptor mediated responsiveness of human and rat atria. Diabetes Res Clin Pract. 1998, 40: 113-22. 10.1016/S0168-8227(98)00034-5.CrossRefPubMed
9.
go back to reference Bidasee KR, Dinçer ÜD, Besch HR: Ryanodine receptor dysfunction in hearts of streptozotocin-induced diabetic rat hearts. Mol Pharmacol. 2001, 60: 1-9. Bidasee KR, Dinçer ÜD, Besch HR: Ryanodine receptor dysfunction in hearts of streptozotocin-induced diabetic rat hearts. Mol Pharmacol. 2001, 60: 1-9.
10.
go back to reference Bristow MR, Minobe WA, Raynolds MV, Port JD, Rasmussen R, Ray PE, Feldman AM: Reduced beta 1 receptor messenger RNA abundance in the failing human heart. J Clin Invest. 1993, 92: 2737-2745.PubMedCentralCrossRefPubMed Bristow MR, Minobe WA, Raynolds MV, Port JD, Rasmussen R, Ray PE, Feldman AM: Reduced beta 1 receptor messenger RNA abundance in the failing human heart. J Clin Invest. 1993, 92: 2737-2745.PubMedCentralCrossRefPubMed
11.
go back to reference Fowler MB, Laser JA, Hopkins GL, Minobe W, Bristow MR: Assessment of the beta-adrenergic receptor pathway in the intact failing human heart: progressive receptor down-regulation and subsensitivity to agonist response. Circulation. 1986, 74: 1290-302.CrossRefPubMed Fowler MB, Laser JA, Hopkins GL, Minobe W, Bristow MR: Assessment of the beta-adrenergic receptor pathway in the intact failing human heart: progressive receptor down-regulation and subsensitivity to agonist response. Circulation. 1986, 74: 1290-302.CrossRefPubMed
12.
go back to reference Schotten U, Filzmaier K, Borghardt B, Kulka S, Schoendube F, Schumacher C, Hanrath P: Changes of beta-adrenergic signaling in compensated human cardiac hypertrophy depend on the underlying disease. Am J Physiol Heart Circ Physiol. 2000, 278: H2076-83.PubMed Schotten U, Filzmaier K, Borghardt B, Kulka S, Schoendube F, Schumacher C, Hanrath P: Changes of beta-adrenergic signaling in compensated human cardiac hypertrophy depend on the underlying disease. Am J Physiol Heart Circ Physiol. 2000, 278: H2076-83.PubMed
13.
go back to reference Freeman K, Lerman I, Kranias EG, Bohlmeyer T, Bristow MR, Lefkowitz RJ, Iaccarino G, Koch WJ, Leinwand LA: Alterations in cardiac adrenergic signaling and calcium cycling differentially affect the progression of cardiomyopathy. J Clin Invest. 2001, 107 (8): 967-74.PubMedCentralCrossRefPubMed Freeman K, Lerman I, Kranias EG, Bohlmeyer T, Bristow MR, Lefkowitz RJ, Iaccarino G, Koch WJ, Leinwand LA: Alterations in cardiac adrenergic signaling and calcium cycling differentially affect the progression of cardiomyopathy. J Clin Invest. 2001, 107 (8): 967-74.PubMedCentralCrossRefPubMed
15.
go back to reference Lefkowitz RJ, Rockman HA, Koch WJ: Catecholamines, cardiac beta-adrenergic receptors, and heart failure. Circulation. 2000, 101: 1634-7.CrossRefPubMed Lefkowitz RJ, Rockman HA, Koch WJ: Catecholamines, cardiac beta-adrenergic receptors, and heart failure. Circulation. 2000, 101: 1634-7.CrossRefPubMed
16.
go back to reference Paulson DJ, Shetlar D, Light KE: Catecholamine levels in the heart, serum and adrenals of experimental diabetic rats. Fed Proc. 1980, 39: 637. Paulson DJ, Shetlar D, Light KE: Catecholamine levels in the heart, serum and adrenals of experimental diabetic rats. Fed Proc. 1980, 39: 637.
17.
go back to reference Christensen NJ: Plasma norepinephrine and epinephrine in untreated diabetics during fasting and after insulin administration. Diabetes. 1974, 23: 1-8.CrossRefPubMed Christensen NJ: Plasma norepinephrine and epinephrine in untreated diabetics during fasting and after insulin administration. Diabetes. 1974, 23: 1-8.CrossRefPubMed
18.
go back to reference Brodde OE, O'Hara N, Zerkowski HR, Rohm N: Human cardiac beta-adrenoceptors: both beta 1- and beta 2-adrenoceptors are functionally coupled to the adenylate cyclase in right atrium. J Cardiovasc Pharmacol. 1984, 6: 1184-91.CrossRefPubMed Brodde OE, O'Hara N, Zerkowski HR, Rohm N: Human cardiac beta-adrenoceptors: both beta 1- and beta 2-adrenoceptors are functionally coupled to the adenylate cyclase in right atrium. J Cardiovasc Pharmacol. 1984, 6: 1184-91.CrossRefPubMed
19.
go back to reference Kaumann AJ: Four β-AR subtypes in the mammalian heart. Trends Pharmacol Sci. 1997, 18: 70-76. 10.1016/S0165-6147(96)01033-4.CrossRefPubMed Kaumann AJ: Four β-AR subtypes in the mammalian heart. Trends Pharmacol Sci. 1997, 18: 70-76. 10.1016/S0165-6147(96)01033-4.CrossRefPubMed
20.
go back to reference Brodde OE, Michel MC: Adrenergic and muscarinic receptors in the human heart. Pharmacol Rev. 1999, 51: 651-90.PubMed Brodde OE, Michel MC: Adrenergic and muscarinic receptors in the human heart. Pharmacol Rev. 1999, 51: 651-90.PubMed
21.
go back to reference Rodefeld MD, Beau SL, Schuessler RB, Boineau JP, Saffitz JE: Beta adrenergic and muscarinic cholinergic receptor densities in the human sinoatrial node: Identification of a high beta 2-adrenergic receptor density. J Cardiovasc Electrophysiol. 1996, 7: 1039-1049.CrossRefPubMed Rodefeld MD, Beau SL, Schuessler RB, Boineau JP, Saffitz JE: Beta adrenergic and muscarinic cholinergic receptor densities in the human sinoatrial node: Identification of a high beta 2-adrenergic receptor density. J Cardiovasc Electrophysiol. 1996, 7: 1039-1049.CrossRefPubMed
22.
23.
go back to reference Brodde OE, Zerkowski HR, Schranz D, Broede-Sitz A, Michel-Reher M, Schafer-Beisenbusch E, Piotrowski JA, Oelert H: Age-dependent changes in the β-Adrenoceptor-G Protein(s)-Adenylyl Cyclase system in human right atrium. J Cardiovasc Pharmacol. 1995, 26: 20-6.CrossRefPubMed Brodde OE, Zerkowski HR, Schranz D, Broede-Sitz A, Michel-Reher M, Schafer-Beisenbusch E, Piotrowski JA, Oelert H: Age-dependent changes in the β-Adrenoceptor-G Protein(s)-Adenylyl Cyclase system in human right atrium. J Cardiovasc Pharmacol. 1995, 26: 20-6.CrossRefPubMed
24.
go back to reference Brian D Lowes, Wayne Minobe, William T Abraham, Mona N Rizeq, Teresa J Bohlmeyer, Robert A Quaife, Robert L Roden, Darin L Dutcher, Alastair D Robertson, Norbert F Voelkel, David B Badesch, Bertron M Groves, Edward M Gilbert, Michael R Bristow: Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in. J Clin Invest. 1997, 100: 2315-24.CrossRef Brian D Lowes, Wayne Minobe, William T Abraham, Mona N Rizeq, Teresa J Bohlmeyer, Robert A Quaife, Robert L Roden, Darin L Dutcher, Alastair D Robertson, Norbert F Voelkel, David B Badesch, Bertron M Groves, Edward M Gilbert, Michael R Bristow: Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in. J Clin Invest. 1997, 100: 2315-24.CrossRef
Metadata
Title
Decreased expression of β1- and β2-adrenoceptors in human diabetic atrial appendage
Authors
U Deniz Dinçer
Şahika Güner
Aydin Tay
Ebru Arioğlu
Atilay Taşdelen
Sait Aşlamaci
Keshore R Bidasee
Publication date
01-12-2003
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2003
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-2-6

Other articles of this Issue 1/2003

Cardiovascular Diabetology 1/2003 Go to the issue