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English Abstract
Journal Article
[At the heart of diabetic cardiomyopathy: Bscl2 knockout mice to investigate glucotoxicity].
Médecine Sciences : M/S 2018 June
Type 2 diabetes mellitus (T2DM) is a well-recognized independent risk factor for heart failure (HF). T2DM is associated with altered cardiac energy metabolism, leading to ectopic lipid accumulation and glucose overload. However, the relative contribution of these two parameters remains unclear. In order to get new insight into the mechanism involved in diabetic cardiomyopathy, the cardiac phenotype of a unique T2DM mice model has been performed: the seipin knockout mice (SKO). Cardiac phenotyping revealed a diastolic dysfunction associated with hyperglycemia in these mice with a chronic activation of the hexosamine biosynthetic pathway (HBP), suggesting a glucose overload. An inhibitor of the renal sodium/glucose cotransporter 2 (SGLT2), dapagliflozin, successfully prevented the development of cardiomyopathy in SKO mice. This is particularly relevant, given that SGLT2i treatment reduces cardiovascular event in T2DM patients. Therefore, glucose lowering appears an important therapeutic target to prevent cardiac dysfunction associated with T2DM.
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