Effects of Obesity and Diabetes on Excitation-Contraction Coupling in Zucker Rat Cardiomyocytes

Abstract

Introduction

Diabetes mellitus (DM) is a serious global health problem and obesity is a major risk factor for DM. Cardiovascular complications are a major cause of morbidity and mortality in diabetic patients and electromechanical dysfunction has been widely reported in the diabetic heart. The aim of this study was to investigate the effects of obesity and diabesity on ventricular myocyte shortening and Ca²⁺ signaling in Zucker fatty (ZF) and Zucker diabetic fatty (ZDF) rats, compared to Zucker lean (ZL) rats.

Materials and Methods

Ventricular myocytes were isolated by enzymatic and mechanical dispersal. Myocyte shortening, L-type Ca²⁺ current, and intracellular Ca²⁺ dynamics were investigated with video imaging, whole cell patch clamp, and fluorescence photometry techniques, respectively.

Results

Time to peak (TPK) shortening was prolonged in ZDF (158.59 ± 3.05 ms) compared to ZF (130.33 ± 2.57 ms) and ZL (126.54 ± 3.09 ms) myocytes. The TPK Ca²⁺ transient was prolonged in ZF (67.26 ± 5.69 ms) compared to ZL (51.54 ± 2.32 ms) myocytes and the time to half (THALF) decay of the Ca²⁺ transient was prolonged in ZDF (155.35 ± 2.92 ms) compared to ZF (131.11 ± 3.26 ms) and ZL (129.17 ± 3.12 ms) myocytes. TPK and THALF decay of caffeine-evoked Ca²⁺ transients were prolonged in ZDF compared to ZF and ZL myocytes.

Conclusion

Although the amplitude of shortening was generally well preserved in ZF and ZDF compared to ZL myocytes, the TPK shortening was prolonged in ZDF myocytes, which might partly be explained by defective uptake and release of sarcoplasmic reticulum Ca²⁺ in ventricular myocytes from the ZDF rat.

Keywords

ventricular myocytes - shortening - intracellular Ca²⁺ - L-type Ca²⁺ current - Zucker fatty rat - Zucker diabetic fatty rat - Zucker lean rat

Authors' Contributions

F.H. secured funding and made substantial contributions to conception and design, drafting, and revising the article. A.S. and M.Q. made substantial contributions to acquisition of data and analysis of data. A.S. and A.S. made substantial contributions to interpretation and graphical representation of data. All authors contributed to the writing and revision of the manuscript. All authors approve the final version to be published.

Compliance with Ethical Principles

Ethical approval for this study was obtained from the Animal Ethics Committee, College of Medicine & Health Sciences, United Arab Emirates University.

Publikationsverlauf

Artikel online veröffentlicht:
19. Mai 2025

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