Effect of Metformin on T2D-Induced MAM Ca2+ Uncoupling and Contractile Dysfunction in an Early Mouse Model of Diabetic HFpEF

International Journal of Molecular Sciences

Maya Dia¹  Helene Thibault¹  Melanie Paillard¹  Christelle Leon¹  Ludovic Gomez¹  Nadia Bendridi²  Stephanie Chanon²  Jennifer Rieusset² 

[1] Laboratoire CarMeN—IRIS Team, INSERM, INRA, Université Claude Bernard Lyon-1, INSA-Lyon, Univ-Lyon, 69500 Bron, France;Laboratoire CarMeN—MERISM Team, INSERM, INRA, Université Claude Bernard Lyon-1, INSA-Lyon, Univ-Lyon, 69921 Oullins, France;

关键词: diabetic cardiomyopathy;    heart failure;    type 2 diabetes;    reticulum-mitochondria interactions;    Ca²⁺ signaling;   

DOI  :  10.3390/ijms23073569

来源: DOAJ

【 摘 要 】

Diabetic cardiomyopathy (DCM) is a leading complication in type 2 diabetes patients. Recently, we have shown that the reticulum-mitochondria Ca²⁺ uncoupling is an early and reversible trigger of the cardiac dysfunction in a diet-induced mouse model of DCM. Metformin is a first-line antidiabetic drug with recognized cardioprotective effect in myocardial infarction. Whether metformin could prevent the progression of DCM remains not well understood. We therefore investigated the effect of a chronic 6-week metformin treatment on the reticulum-mitochondria Ca²⁺ coupling and the cardiac function in our high-fat high-sucrose diet (HFHSD) mouse model of DCM. Although metformin rescued the glycemic regulation in the HFHSD mice, it did not preserve the reticulum-mitochondria Ca²⁺ coupling either structurally or functionally. Metformin also did not prevent the progression towards cardiac dysfunction, i.e., cardiac hypertrophy and strain dysfunction. In summary, despite its cardioprotective role, metformin is not sufficient to delay the progression to early DCM.

【 授权许可】

Unknown