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. 2025 Apr;21(3):849-858.
doi: 10.1007/s12015-024-10839-8. Epub 2025 Jan 22.

Empagliflozin Reduces High Glucose-Induced Cardiomyopathy in hiPSC-Derived Cardiomyocytes : Glucose-induced Lipotoxicity in hiPSC-Derived Cardiomyocytes

Hsiu-Hui Tsai  1 , Fu-Chih Hsiao  2 , Alice L Yu  1   3 , Jyuhn-Huarng Juang  4 , John Yu  5 , Pao-Hsien Chu  6   7
Affiliations

Empagliflozin Reduces High Glucose-Induced Cardiomyopathy in hiPSC-Derived Cardiomyocytes : Glucose-induced Lipotoxicity in hiPSC-Derived Cardiomyocytes

Hsiu-Hui Tsai et al. Stem Cell Rev Rep. 2025 Apr.

Abstract

Human-induced pluripotent stem cell (hiPSC) technology has been applied in pathogenesis studies, drug screening, tissue engineering, and stem cell therapy, and patient-specific hiPSC-derived cardiomyocytes (hiPSC-CMs) have shown promise in disease modeling, including diabetic cardiomyopathy. High glucose (HG) treatment induces lipotoxicity in hiPSC-CMs, as evidenced by changes in cell size, beating rate, calcium handling, and lipid accumulation. Empagliflozin, an SGLT2 inhibitor, effectively mitigates the hypertrophic changes, abnormal calcium handling, and contractility impairment induced by HG. Glucose concentration influences SGLT2 expression in cardiomyocytes, highlighting its potential role in diabetic cardiomyopathy. These findings support the potential utility of hiPSC-CMs in studying diabetic cardiomyopathy and the efficacy of empagliflozin in ameliorating HG-induced cardiomyocyte dysfunction. Such research may advance developments in precision medicine and therapeutic interventions for patients with diabetic cardiomyopathy.

Keywords: Cardiomyocyte; Diabetic cardiomyopathy; Empagliflozin; HiPSC.

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Conflict of interest statement

Declarations. Ethical Approval: The study received approval from the Institutional Review Board of Chang-Gung Memorial Hospital (approval number: #202101606B0). Consent to Participate: Peripheral blood mononuclear cells (PBMCs) were collected from four subjects after obtaining written informed consent: one healthy subject and three diabetic patients (one type 1 without as well as one type 1 and one type 2 with diabetic cardiomyopathy and heart failure with HFpEF). Consent to Publish: Not applicable. Competing Interests: All authors disclose any potential conflicts of interest and there are no competing interests at all.

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