Background: Diabetic cardiomyopathy (DCM) pathogenesis is a common complication of diabetes, but effective treatments remain limited. Mitochondrial-derived peptide MOTS-c has shown therapeutic promise in animal models of various heart diseases, but its efficacy in DCM is unknown. This study investigates the effects of MOTS-c treatment in a mouse model of type 1 diabetes-induced DCM.
Methods: Type 1 diabetes (T1DM) was induced in mice by streptozotocin (STZ) injection. After diabetes establishment, the mice were randomly dividend into two groups treated with or without MOTS-c peptide, which was administered subcutaneously by osmotic pump for 12 weeks. At the end of the experiment, cardiac function, histology, and molecular changes were determined.
Results: The results showed that diabetic mice exhibited significant cardiac dysfunction, dilatation, and adverse cardiac remodeling. MOTS-c treatment markedly ameliorated these diabetes-associated myocardial function and structure abnormalities. Additionally, MOTS-c reversed AMPK signaling deactivation and inhibited inflammation in the diabetic heart.
Conclusions: Our data demonstrated a protective effect of MOTS-c against diabetic cardiomyopathy potentially by activating the AMPK pathway and inhibiting inflammation. These findings demonstrate the therapeutic efficacy of MOTS-c for diabetic cardiomyopathy and warrant further investigation into its clinical potential.
Keywords: AMPK; Cardiac remodeling; Diabetic cardiomyopathy; Inflammation; MOTS-c.
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.