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 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.

Keywords: 3,5,3′ tri-iodothyronine; AKT; AMI; AMP-activated protein kinase; AMPK; ANOVA; DM; DTT; Diabetes; ECG; EDTA; EF%; EGTA; ERK; HRP; Insulin; KCl; Kinase signaling; L-thyroxine; LV; LVIDd; LVIDs; LVPW; Myocardial infarction; NS; PMSF; RV; S.E.M; SDS-PAGE; SI; STZ; T3; T4; TH; TRα1; TSH; Thyroid hormone; WTI; acute myocardial infarction; diabetes mellitus; dithiothreitol; ejection fraction; electrocardiogram; ethylene glycol tetraacetic acid; ethylenediaminetetraacetic acid; extracellular signal-regulated kinase; horseradish peroxidase; i.p; intraperitoneal; left ventricle; left ventricular internal diameter at the diastolic phase; left ventricular internal diameter at the systolic phase; mTOR; mammalian target of rapamycin; non-significant; one-way analysis of variance; phenylmethanesulfonylfluoride; posterior wall thickness at the diastolic phase; potassium chloride; protein kinase B; right ventricle; sodium dodecyl sulfate polyacrylamide gel electrophoresis; sphericity index; standard error of mean; streptozotocin; thyroid hormone; thyroid hormone receptor alpha1; thyroid stimulating hormone; wall tension index.