Background and purpose
Muscle protein catabolism in patients with diabetic nephropathy (DN)
Purpose
Muscle protein catabolism in patients with diabetic nephropathy (DN)
Results
Butyrate levels in DN patients were significantly decreased. In db/db mice, supplementing normal diet with butyrate improved intestinal barrier function. Concurrently, butyrate alleviated muscle atrophy, promoted PI3K/Akt/mTOR signalling, and suppressed oxidative stress and autophagy in skeletal muscle of db/db mice, and in HG/LPS-exposed C2C12 cells. Further, FFA2 receptors, key components of SCFA signalling, were decreased in skeletal muscle of db/db mice and in HG/LPS-exposed C2C12 cells. Overexpression of FFA2 receptors activated PI3K/Akt/mTOR signalling and inhibited oxidative stress and autophagy in HG/LPS-exposed C2C12 cells. Silencing of FFA2 blocked PI3K/Akt/mTOR signalling that was improved by butyrate, as well as the suppression of oxidative stress and reduction of autophagy.