| Attenuation of beta2-adrenergic receptors and homocysteine metabolic enzymes cause diabetic cardiomyopathy. | |
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MedLine Citation:
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PMID: 20836991 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although adrenergic receptors (AR) and hyperhomocysteinemia (HHcy) are implicated in heart failure, their role in diabetic cardiomyopathy is not completely understood. We tested the hypothesis that glucose mediated depletion of beta2-AR and HHcy impair contractile function of cardiomyocytes leading to diabetic cardiomyopathy. To prove the hypothesis, cardiac function was assessed in 12week male diabetic Ins2+/- Akita and C57BL/6J mice by echocardiography, pressure-volume loop, and contractile function of cardiomyocytes. The results revealed cardiac dysfunction in Akita. To investigate the mechanism, the levels of beta2-AR, GLUT4, sarcoplasmic reticulum calcium ATP-ase-isoform 2 (SERCA-2) and homocysteine (Hcy) metabolic enzymes-cystathionine beta synthase (CBS), cystathionine gamma lyase (CTH), and methyl tetrahydrofolate reductase (MTHFR) were determined in the heart. It revealed down-regulation of beta2-AR, GLUT4, SERCA-2, CBS, CTH, and MTHFR in Akita. Attenuation of beta2-AR in hyperglycemic condition was also confirmed in cardiomyocytes at in vitro level. Interestingly, the ex vivo treatment of cardiomyocytes with beta2-AR antagonist deteriorated whereas beta-AR agonist ameliorated contractile function. It points to the involvement of beta2-AR in diabetic cardiomyopathy. We conclude that degradation of beta2-AR and impairment of Hcy metabolism is implicated in diabetic cardiomyopathy. |
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Authors:
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Paras Kumar Mishra; Srikanth Givvimani; Naira Metreveli; Suresh C Tyagi |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-09-15 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 401 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-18 Completed Date: 2010-11-30 Revised Date: 2011-10-17 |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 175-81 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Physiology & Biophysics, School of Medicine, University of Louisville, Louisville, KY 40202, USA. pkmish01@louisville.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cardiomyopathies / enzymology, etiology* Cystathionine beta-Synthase / deficiency* Cystathionine gamma-Lyase / deficiency* Diabetes Mellitus, Experimental / complications* Folic Acid / pharmacology Glucose / pharmacology Glucose Transporter Type 4 / metabolism Heart Failure / enzymology, etiology Homocysteine / metabolism* Hyperglycemia / chemically induced, genetics Hyperhomocysteinemia / enzymology, etiology* Male Methylenetetrahydrofolate Reductase (NADPH2) / deficiency* Mice Mice, Inbred C57BL Mice, Mutant Strains Myocardial Contraction / drug effects, physiology Myocytes, Cardiac / drug effects, enzymology, physiology Receptors, Adrenergic, beta-2 / agonists, antagonists & inhibitors, deficiency* Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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HL-71010/HL/NHLBI NIH HHS; HL-74185/HL/NHLBI NIH HHS; HL-88012/HL/NHLBI NIH HHS; R01 HL071010-07/HL/NHLBI NIH HHS; R01 HL074185-07/HL/NHLBI NIH HHS; R01 HL088012-03/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Glucose Transporter Type 4; 0/Receptors, Adrenergic, beta-2; 0/Slc2a4 protein, mouse; 454-28-4/Homocysteine; 50-99-7/Glucose; 59-30-3/Folic Acid; EC 1.5.1.20/Methylenetetrahydrofolate Reductase (NADPH2); EC 3.6.3.8/Atp2a2 protein, mouse; EC 3.6.3.8/Sarcoplasmic Reticulum Calcium-Transporting ATPases; EC 4.2.1.22/Cystathionine beta-Synthase; EC 4.4.1.1/Cystathionine gamma-Lyase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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