Key result
Metformin fails to prevent cardiac dysfunction or preserve organelle calcium coupling in early diabetic HFpEF.
Why the study?
Whether metformin could prevent the progression of diabetic cardiomyopathy remained not well understood.
Does metformin prevent reticulum-mitochondria Ca2+ uncoupling and contractile dysfunction in an early mouse model of diabetic HFpEF?
Does metformin prevent reticulum-mitochondria Ca2+ uncoupling and contractile dysfunction in an early mouse model of diabetic HFpEF?
Despite its known cardioprotective effects in myocardial infarction and glycemic benefits, metformin does not prevent the progression of early diabetic cardiomyopathy or preserve MAM Ca2+ coupling in a preclinical HFpEF model.
Metformin does not prevent cardiac dysfunction in diabetic HFpEF mice despite glycemic benefit; hypothesis-generating for MAM Ca2+ coupling as a target.
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.
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Dia et al. (2022) studied Diabetic Cardiomyopathy (early HFpEF) (n=42). Metformin vs. Vehicle (0.5% methylcellulose) was evaluated on Reticulum-mitochondria Ca2+ coupling and cardiac function (hypertrophy, strain dysfunction). Metformin treatment for 6 weeks improved glycemic control but failed to preserve reticulum-mitochondria Ca2+ coupling or prevent cardiac dysfunction in an early mouse model of diabetic HFpEF.
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