PMID- 23709595
OWN - NLM
STAT- MEDLINE
DCOM- 20131017
LR  - 20200930
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Linking)
VI  - 305
IP  - 3
DP  - 2013 Aug 1
TI  - Glucagon-like peptide-1 receptor activation reverses cardiac remodeling via 
      normalizing cardiac steatosis and oxidative stress in type 2 diabetes.
PG  - H295-304
LID - 10.1152/ajpheart.00990.2012 [doi]
AB  - Glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 (Ex-4) is a remedy 
      for type 2 diabetes mellitus (T2DM). Ex-4 ameliorates cardiac dysfunction induced 
      by myocardial infarction in preclinical and clinical settings. However, it 
      remains unclear whether Ex-4 may modulate diabetic cardiomyopathy. We tested the 
      impact of Ex-4 on two types of diabetic cardiomyopathy models, genetic (KK) and 
      acquired T2DM induced by high-fat diet [diet-induced obesity (DIO)], to clarify 
      whether Ex-4 may combat independently of etiology. Each type of mice was divided 
      into Ex-4 (24 nmol.kg(-1).day(-1) for 40 days; KK-ex4 and DIO-ex4) and vehicle 
      (KK-v and DIO-v) groups. Ex-4 ameliorated systemic and cardiac insulin resistance 
      and dyslipidemia in both T2DM models. T2DM mice exhibited systolic (DIO-v) and 
      diastolic (DIO-v and KK-v) left ventricular dysfunctions, which were restored by 
      Ex-4 with reduction in left ventricular hypertrophy. DIO-v and KK-v exhibited 
      increased myocardial fibrosis and steatosis (lipid accumulation), in which were 
      observed cardiac mitochondrial remodeling and enhanced mitochondrial oxidative 
      damage. Ex-4 treatment reversed these cardiac remodeling and oxidative stress. 
      Cytokine array revealed that Ex-4-sensitive inflammatory cytokines were ICAM-1 
      and macrophage colony-stimulating factor. Ex-4 ameliorated myocardial oxidative 
      stress via suppression of NADPH oxidase 4 with concomitant elevation of 
      antioxidants (SOD-1 and glutathione peroxidase). In conclusion, GLP-1R agonism 
      reverses cardiac remodeling and dysfunction observed in T2DM via normalizing 
      imbalance of lipid metabolism and related inflammation/oxidative stress.
FAU - Monji, Akio
AU  - Monji A
AD  - Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan.
FAU - Mitsui, Toko
AU  - Mitsui T
FAU - Bando, Yasuko K
AU  - Bando YK
FAU - Aoyama, Morihiko
AU  - Aoyama M
FAU - Shigeta, Toshimasa
AU  - Shigeta T
FAU - Murohara, Toyoaki
AU  - Murohara T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130524
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Glp1r protein, mouse)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Icam1 protein, mouse)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Glucagon)
RN  - 0 (Venoms)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - 9P1872D4OL (Exenatide)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
RN  - EC 1.15.1.1 (Sod1 protein, mouse)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.15.1.1 (Superoxide Dismutase-1)
RN  - EC 1.6.3.- (NADPH Oxidase 4)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.- (Nox4 protein, mouse)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy/genetics
MH  - Diabetic Cardiomyopathies/blood/diagnostic imaging/*drug therapy/physiopathology
MH  - Diet, High-Fat
MH  - Disease Models, Animal
MH  - Dyslipidemias/blood/drug therapy
MH  - Echocardiography, Doppler
MH  - Exenatide
MH  - Fibrosis
MH  - Glucagon-Like Peptide-1 Receptor
MH  - Glutathione Peroxidase/metabolism
MH  - Hypertrophy, Left Ventricular/blood/drug therapy/physiopathology
MH  - Hypoglycemic Agents/administration & dosage/*pharmacology
MH  - Inflammation Mediators/metabolism
MH  - Infusions, Subcutaneous
MH  - Insulin Resistance
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Lipid Metabolism/*drug effects
MH  - Macrophage Colony-Stimulating Factor/metabolism
MH  - Male
MH  - Mice
MH  - Mitochondria, Heart/drug effects/metabolism/pathology
MH  - Myocardium/*metabolism/pathology
MH  - NADPH Oxidase 4
MH  - NADPH Oxidases/metabolism
MH  - Oxidative Stress/*drug effects
MH  - Peptides/administration & dosage/*pharmacology
MH  - Receptors, Glucagon/*agonists/metabolism
MH  - Superoxide Dismutase/metabolism
MH  - Superoxide Dismutase-1
MH  - Time Factors
MH  - Venoms/administration & dosage/*pharmacology
MH  - Ventricular Dysfunction, Left/blood/drug therapy/physiopathology
MH  - Ventricular Function, Left/drug effects
MH  - Ventricular Remodeling/*drug effects
OTO - NOTNLM
OT  - diabetes mellitus
OT  - glucagon-like peptide-1
OT  - insulin resistance
OT  - mitochondria
OT  - oxidative stress
EDAT- 2013/05/28 06:00
MHDA- 2013/10/18 06:00
CRDT- 2013/05/28 06:00
PHST- 2013/05/28 06:00 [entrez]
PHST- 2013/05/28 06:00 [pubmed]
PHST- 2013/10/18 06:00 [medline]
AID - ajpheart.00990.2012 [pii]
AID - 10.1152/ajpheart.00990.2012 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2013 Aug 1;305(3):H295-304. doi: 
      10.1152/ajpheart.00990.2012. Epub 2013 May 24.