Abstract | BACKGROUND: METHODS: Two weeks post-MI, male Sprague-Dawley rats were treated with GLP-1 (2.5 or 25 pmol/kg/min), AC3174 (1.7 or 5 pmol/kg/min) or vehicle via subcutaneous infusion for 11 weeks. Cardiac function and morphology were assessed by echocardiography during treatment. Metabolic, hemodynamic, exercise-capacity, and body composition measurements were made at study end. RESULTS: Compared with vehicle-treated rats with CHF, GLP-1 or AC3174 significantly improved cardiac function, including left ventricular (LV) ejection fraction, and end diastolic pressure. Cardiac dimensions also improved as evidenced by reduced LV end diastolic and systolic volumes and reduced left atrial volume. Vehicle-treated CHF rats exhibited fasting hyperglycemia and hyperinsulinemia. In contrast, GLP-1 or AC3174 normalized fasting plasma insulin and glucose levels. GLP-1 or AC3174 also significantly reduced body fat and fluid mass and improved exercise capacity and respiratory efficiency. Four of 16 vehicle control CHF rats died during the study compared with 1 of 44 rats treated with GLP-1 or AC3174. The cellular mechanism by which GLP-1 or AC3174 exert cardioprotective effects appears unrelated to changes in GLUT1 or GLUT4 translocation or expression. CONCLUSIONS:
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Authors | Que Liu, Christen Anderson, Anatoly Broyde, Clara Polizzi, Rayne Fernandez, Alain Baron, David G Parkes |
Journal | Cardiovascular diabetology
(Cardiovasc Diabetol)
Vol. 9
Pg. 76
(Nov 16 2010)
ISSN: 1475-2840 [Electronic] England |
PMID | 21080957
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- AC3174
- Blood Glucose
- Cardiotonic Agents
- Glucose Transporter Type 1
- Glucose Transporter Type 4
- Insulin
- Peptides
- Slc2a1 protein, rat
- Slc2a4 protein, rat
- Glucagon-Like Peptide 1
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Topics |
- Animals
- Blood Glucose
(drug effects)
- Cardiotonic Agents
(administration & dosage, pharmacology)
- Chronic Disease
- Disease Models, Animal
- Echocardiography, Doppler, Pulsed
- Exercise Tolerance
(drug effects)
- Glucagon-Like Peptide 1
(administration & dosage, pharmacology)
- Glucose Transporter Type 1
(metabolism)
- Glucose Transporter Type 4
(metabolism)
- Heart Failure
(blood, drug therapy, etiology, physiopathology)
- Hemodynamics
(drug effects)
- Infusions, Subcutaneous
- Insulin
(blood)
- Male
- Myocardial Infarction
(blood, complications, drug therapy, physiopathology)
- Myocardium
(metabolism)
- Peptides
(administration & dosage, pharmacology)
- Rats
- Rats, Sprague-Dawley
- Stroke Volume
(drug effects)
- Time Factors
- Ventricular Function, Left
(drug effects)
- Ventricular Pressure
(drug effects)
- Ventricular Remodeling
(drug effects)
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