Apolipoprotein A-I mimetic peptide L-4F prevents myocardial and coronary dysfunction in diabetic mice

Diabetes is a major health problem associated with adverse cardiovascular outcomes. The apolipoprotein A‐I mimetic peptide L‐4F is a putative anti‐diabetic drug, has antioxidant and anti‐inflammatory proprieties and improves endothelial function. In obese mice L‐4F increases adiponectin levels, impr...

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Bibliographic Details
Published in:Journal of cellular biochemistry 2011-09, Vol.112 (9), p.2616-2626
Main Authors: Vecoli, C., Cao, J., Neglia, D., Inoue, K., Sodhi, K., Vanella, L., Gabrielson, K.K., Bedja, D., Paolocci, N., L'Abbate, A., Abraham, N.G.
Format: Article
Language:English
Subjects:
Adenylate Kinase - metabolism
Adiponectin
Adiponectin - blood
Animals
Blood Glucose - metabolism
Body Weight - drug effects
Cardiotonic Agents - pharmacology
Cardiotonic Agents - therapeutic use
Cytokines - blood
Diabetes
Diabetes Mellitus, Experimental - complications
Diabetes Mellitus, Experimental - drug therapy
Diabetes Mellitus, Experimental - physiopathology
Heart - drug effects
Heart - physiopathology
Heart Function Tests
Heme oxygenase
Heme Oxygenase-1 - metabolism
Inflammation
Insulin sensitivity
Mice
Mice, Inbred C57BL
Mice, Obese
Myocardium - enzymology
Myocardium - metabolism
Nitric Oxide Synthase - metabolism
Oxidative STRESS
Peptides - pharmacology
Peptides - therapeutic use
Superoxides - metabolism
Ventricular Dysfunction, Left - etiology
Ventricular Dysfunction, Left - physiopathology
Ventricular Dysfunction, Left - prevention & control
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Summary:Diabetes is a major health problem associated with adverse cardiovascular outcomes. The apolipoprotein A‐I mimetic peptide L‐4F is a putative anti‐diabetic drug, has antioxidant and anti‐inflammatory proprieties and improves endothelial function. In obese mice L‐4F increases adiponectin levels, improving insulin sensitivity, and reducing visceral adiposity. We hypothesized that the pleiotropic actions of L‐4F can prevent heart and coronary dysfunction in a mouse model of genetically induced Type II diabetes. We treated db/db mice with either L‐4F or vehicle for 8 weeks. Trans‐thoracic echocardiography was performed; thereafter, isolated hearts were subjected to ischemia/reperfusion (IR). Glucose, insulin, adiponectin, and pro‐inflammatory cytokines (IL‐1β, TNF‐α, MCP‐1) were measured in plasma and HO‐1, pAMPK, peNOS, iNOS, adiponectin, and superoxide in cardiac tissue. In db/db mice L‐4F decreased accumulation of subcutaneous and total fat, and increased insulin sensitivity and adiponectin levels while lowering inflammatory cytokines (P 
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.23188