PMID- 20836991
OWN - NLM
STAT- MEDLINE
DCOM- 20101130
LR  - 20220310
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 401
IP  - 2
DP  - 2010 Oct 15
TI  - Attenuation of beta2-adrenergic receptors and homocysteine metabolic enzymes 
      cause diabetic cardiomyopathy.
PG  - 175-81
LID - 10.1016/j.bbrc.2010.09.006 [doi]
AB  - 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.
CI  - Copyright (c) 2010 Elsevier Inc. All rights reserved.
FAU - Mishra, Paras Kumar
AU  - Mishra PK
AD  - Department of Physiology & Biophysics, School of Medicine, University of 
      Louisville, Louisville, KY 40202, USA. pkmish01@louisville.edu
FAU - Givvimani, Srikanth
AU  - Givvimani S
FAU - Metreveli, Naira
AU  - Metreveli N
FAU - Tyagi, Suresh C
AU  - Tyagi SC
LA  - eng
GR  - R01 HL074185/HL/NHLBI NIH HHS/United States
GR  - R01 HL108621/HL/NHLBI NIH HHS/United States
GR  - R01 HL071010/HL/NHLBI NIH HHS/United States
GR  - R01 HL088012/HL/NHLBI NIH HHS/United States
GR  - HL-74185/HL/NHLBI NIH HHS/United States
GR  - HL-88012/HL/NHLBI NIH HHS/United States
GR  - HL-71010/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100915
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Adrenergic beta-2 Receptor Agonists)
RN  - 0 (Adrenergic beta-2 Receptor Antagonists)
RN  - 0 (Glucose Transporter Type 4)
RN  - 0 (Receptors, Adrenergic, beta-2)
RN  - 0 (Slc2a4 protein, mouse)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 935E97BOY8 (Folic Acid)
RN  - EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2))
RN  - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
RN  - EC 4.4.1.1 (Cystathionine gamma-Lyase)
RN  - EC 7.2.2.10 (Atp2a2 protein, mouse)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adrenergic beta-2 Receptor Agonists
MH  - Adrenergic beta-2 Receptor Antagonists
MH  - Animals
MH  - Cardiomyopathies/enzymology/*etiology
MH  - Cystathionine beta-Synthase/*deficiency
MH  - Cystathionine gamma-Lyase/*deficiency
MH  - Diabetes Mellitus, Experimental/*complications
MH  - Folic Acid/pharmacology
MH  - Glucose/pharmacology
MH  - Glucose Transporter Type 4/metabolism
MH  - Heart Failure/enzymology/etiology
MH  - Homocysteine/*metabolism
MH  - Hyperglycemia/chemically induced/genetics
MH  - Hyperhomocysteinemia/enzymology/*etiology
MH  - Male
MH  - Methylenetetrahydrofolate Reductase (NADPH2)/*deficiency
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Myocardial Contraction/drug effects/physiology
MH  - Myocytes, Cardiac/drug effects/enzymology/physiology
MH  - Receptors, Adrenergic, beta-2/*deficiency
MH  - Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism
PMC - PMC2966019
MID - NIHMS236519
EDAT- 2010/09/15 06:00
MHDA- 2010/12/14 06:00
PMCR- 2011/10/15
CRDT- 2010/09/15 06:00
PHST- 2010/09/01 00:00 [received]
PHST- 2010/09/03 00:00 [accepted]
PHST- 2010/09/15 06:00 [entrez]
PHST- 2010/09/15 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
PHST- 2011/10/15 00:00 [pmc-release]
AID - S0006-291X(10)01681-5 [pii]
AID - 10.1016/j.bbrc.2010.09.006 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2010 Oct 15;401(2):175-81. doi: 
      10.1016/j.bbrc.2010.09.006. Epub 2010 Sep 15.