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

Authors :
Maya Dia
Christelle Leon
Stephanie Chanon
Nadia Bendridi
Ludovic Gomez
Jennifer Rieusset
Helene Thibault
Melanie Paillard
Source :
International Journal of Molecular Sciences, Vol 23, Iss 7, p 3569 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

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.

Details

Language :
English
ISSN :
14220067 and 16616596
Volume :
23
Issue :
7
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.00593f0d4a54a89089ca0e7d780e
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms23073569