Abstract
Aims/hypothesis
Type 2 diabetes is associated with a reduction in skeletal muscle mass; however, how the progression of sarcopenia is induced and regulated remains largely unknown. We aimed to find out whether a specific microRNA (miR) may contribute to skeletal muscle atrophy in type 2 diabetes.
Methods
Adeno-associated virus (AAV)-mediated skeletal muscle miR-193b overexpression in C57BLKS/J mice, and skeletal muscle miR-193b deficiency in db/db mice were used to explore the function of miR-193b in muscle loss. In C57BL/6 J mice, tibialis anterior-specific deletion of 3-phosphoinositide-dependent protein kinase-1 (PDK1), mediated by in situ AAV injection, was used to confirm whether miR-193b regulates muscle growth through PDK1. Serum miR-193b levels were also analysed in healthy individuals (n = 20) and those with type 2 diabetes (n = 20), and correlations of miR-193b levels with HbA1c, fasting blood glucose (FBG), body composition, triacylglycerols and C-peptide were assessed.
Results
In this study, we found that serum miR-193b levels increased in individuals with type 2 diabetes and negatively correlated with muscle mass in these participants. Functional studies further showed that AAV-mediated overexpression of miR-193b induced muscle loss and dysfunction in healthy mice. In contrast, suppression of miR-193b attenuated muscle loss and dysfunction in db/db mice. Mechanistic analysis revealed that miR-193b could target Pdk1 expression to inactivate the Akt/mammalian target of rapamycin (mTOR)/p70S6 kinase (S6K) pathway, thereby inhibiting protein synthesis. Therefore, knockdown of PDK1 in healthy mice blocked miR-193b-induced inactivation of the Akt/mTOR/S6K pathway and impairment of muscle growth.
Conclusions/interpretation
Our results identified a previously unrecognised role of miR-193b in muscle function and mass that could be a potential therapeutic target for treating sarcopenia.
Graphical abstract
Corrigendum to “Type 2 diabetes-induced overactivation of P300 contributes to skeletal muscle atrophy by inhibiting autophagic flux” [Life Sci. 2020 Oct 1;258:118243]
