Acute Exercise Promptly Normalizes Myocardial Myosin Heavy-Chain Isoform mRNA Composition in Diabetic Rats: Implications for Diabetic Cardiomyopathy

Abstract

Background and Objectives: The acute effects of exercise on the myosin heavy-chain (MHC) isoform mRNA expression and the upstream transcription factors in diabetic and non-diabetic hearts remain unexplored. We aimed to determine the acute effect of a single exercise session on the expression of left ventricular MHC, MHC-α and MHC-β, and thyroid receptor (TR), TR-α1 and TR-β, isoform mRNA in diabetic and non-diabetic rats. Materials and Methods: Sprague-Dawley rats were assigned to four groups: non-diabetic control (CS), diabetic exercise (DIEX), sedentary diabetic (DIS), and non-diabetic exercise (CEX). Diabetes was induced via streptozotocin injection (55 mg/kg). DIEX and CEX rats performed an exercise session (60 min at 50 m/min and 0% grade) 6-7 weeks after diabetes induction. Results: MHC-α mRNA was lower in DIS (p = 0.03) and not different in DIEX (p = 0.1) relative to CS. DIS showed higher MHC-β mRNA than the non-diabetic rats, CS and CEX (p = 0.02 and p = 0.009, respectively). MHC-β mRNA in DIEX was normalized to non-diabetic levels in CS (p = 0.3). TR-α1 was higher in DIS and not different in DIEX relative to CS and CEX (p = 0.03 and p = 1.0, respectively). In CEX, exercise did not change MHC-α, MHC-β, and TR-α1 relative to CS (p = 1.0). TR-β was not different between groups. Conclusion: In conclusion, exercise appears to acutely normalize the myocardial MHC and TR isoform mRNA expression only in the diabetic heart. These responses may induce therapeutic mechanisms other than changing the MHC isoform composition.

Keywords: exercise training; myocardium; myosin isozymes; sedentary lifestyle; thyroid receptors.

Figure 1

Fold change in MHC-α and MHC-β mRNA relative expression in the control sedentary (CS; n = 7), control exercise (CEX; n = 7), diabetic sedentary (DIS; n = 7), and diabetic exercise (DIEX; n = 9) mice. One-way ANOVA followed by multiple comparisons with Bonferroni adjustment was used in analysis. * Significantly different from CS at p < 0.05. # Significantly different from CEX at p < 0.05.

Figure 2

Fold change in TR-α1 and TR-β mRNA relative expression in the control sedentary (CS; n = 7), control exercise (CEX; n = 7), diabetic sedentary (DIS; n = 7), and diabetic exercise (DIEX; n = 9) mice. One-way ANOVA followed by multiple comparisons with Bonferroni adjustment was used in analysis. * Significantly different from DIS at p < 0.05.