Thyroid hormone improves the mechanical performance of the post-infarcted diabetic myocardium: A response associated with up-regulation of Akt/mTOR and AMPK activation

Abstract Objective Thyroid hormone (TH) is shown to be protective against cardiac and pancreatic injury. Thus, this study explored the potential effects of TH treatment on the functional status of the postinfarcted diabetic myocardium. Diabetic patients have worse prognosis after acute myocardial in...

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Bibliographic Details
Published in:	Metabolism, clinical and experimental Vol. 62; no. 10; pp. 1387 - 1393
Main Authors:	Mourouzis, Iordanis, Giagourta, Irini, Galanopoulos, Georgios, Mantzouratou, Polixeni, Kostakou, Erietta, Kokkinos, Alexandros D, Tentolouris, Nikolaos, Pantos, Constantinos
Format:	Journal Article
Language:	English
Published:	New York, NY Elsevier Inc 01-10-2013 Elsevier
Subjects:	AMP-Activated Protein Kinases - metabolism Animals Biological and medical sciences Blood Glucose - metabolism Cardiology. Vascular system Cardiomegaly - blood Cardiomegaly - drug therapy Cardiomegaly - metabolism Cardiomegaly - physiopathology Coronary heart disease Diabetes Diabetes Complications - blood Diabetes Complications - drug therapy Diabetes Complications - metabolism Diabetes Complications - physiopathology Diabetes Mellitus - blood Diabetes Mellitus - metabolism Diabetes Mellitus - physiopathology Diabetes. Impaired glucose tolerance Endocrine pancreas. Apud cells (diseases) Endocrinology & Metabolism Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Feeding. Feeding behavior Fundamental and applied biological sciences. Psychology Heart Heart - drug effects Heart - physiopathology Heart Ventricles - drug effects Heart Ventricles - metabolism Heart Ventricles - physiopathology Insulin Insulin - blood Insulin - metabolism Kinase signaling Male Medical sciences Myocardial infarction Myocardial Infarction - blood Myocardial Infarction - drug therapy Myocardial Infarction - metabolism Myocardial Infarction - physiopathology Myocardium - metabolism Proto-Oncogene Proteins c-akt - metabolism Rats Rats, Wistar Signal Transduction Thyroid hormone Thyroid Hormones - pharmacology TOR Serine-Threonine Kinases - metabolism Up-Regulation Vertebrates: anatomy and physiology, studies on body, several organs or systems Myocardial infarction extracellular signal-regulated kinase thyroid hormone thyroid hormone receptor alpha1 left ventricle HRP LVIDd DM potassium chloride LV thyroid stimulating hormone WTI phenylmethanesulfonylfluoride electrocardiogram KCl ethylenediaminetetraacetic acid horseradish peroxidase STZ mTOR left ventricular internal diameter at the systolic phase AMI EF non-significant TSH standard error of mean i.p Insulin EGTA SDS-PAGE LVPW streptozotocin PMSF TRα1 LVIDs AMPK ethylene glycol tetraacetic acid ERK Kinase signaling RV ejection fraction DTT sodium dodecyl sulfate polyacrylamide gel electrophoresis NS diabetes mellitus sphericity index AMP-activated protein kinase L-thyroxine mammalian target of rapamycin left ventricular internal diameter at the diastolic phase ANOVA SI wall tension index T3 protein kinase B T4 one-way analysis of variance intraperitoneal dithiothreitol ECG AKT EDTA S.E.M posterior wall thickness at the diastolic phase TH right ventricle 3,5,3′ tri-iodothyronine Diabetes acute myocardial infarction Thyroid hormone Endocrinopathy Performance evaluation Diabetes mellitus Cardiovascular disease Activation cAMP-dependent protein kinase Coronary heart disease Myocardial disease Regulation(control) Association Endocrinology
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Summary:	Abstract Objective Thyroid hormone (TH) is shown to be protective against cardiac and pancreatic injury. Thus, this study explored the potential effects of TH treatment on the functional status of the postinfarcted diabetic myocardium. Diabetic patients have worse prognosis after acute myocardial infarction (AMI). Materials/Methods AMI was induced by left coronary ligation in rats previously treated with 35 mg/kg streptozotocin (STZ), (DM-AMI). TH treatment was initiated at 2 weeks after AMI and continued for 6 weeks (DM-AMI + TH), while sham-operated animals served as control (DM-SHAM). Results TH treatment increased cardiac mass, improved wall stress and favorably changed cardiac geometry. TH significantly increased echocardiographic left ventricular ejection fraction (LVEF%): [54.2 (6.5) for DM-AMI + TH vs 37 (2.0) for DM-AMI, p < 0.05]. TH treatment resulted in significantly increased insulin and decreased glucose levels in serum. The ratios of phosphorylated (p)-Akt/total Akt and p-mTOR/total mTOR were increased 2.0 fold and 2.7 fold in DM-AMI + TH vs DM-AMI respectively, p < 0.05. Furthermore, the ratio of p-AMPK/total AMPK was found to be increased 1.6 fold in DM-AMI + TH vs DM-AMI, p < 0.05. Conclusion TH treatment improved the mechanical performance of the post-infarcted myocardium in rats with STZ-induced diabetes, an effect which was associated with Akt/mTOR and AMPK activation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0026-0495 1532-8600
DOI:	10.1016/j.metabol.2013.05.008