Greater filamin C, GSK3α, and GSK3β serine phosphorylation in insulin-stimulated isolated skeletal muscles of calorie restricted 24 month-old rats.

Moderate calorie restriction (CR) can improve insulin-stimulated Akt phosphorylation and glucose uptake in muscles from 24 month-old rats, but the specific Akt substrates linking CR-effects on Akt to glucose uptake and other cellular processes are uncertain. We probed CR's influence on site-specific phosphorylation of five Akt substrates (AS160(Ser588), TBC1D1(Thr596), FLNc(Ser2213), GSK3α(Ser21), and GSK3β(Ser9)) in predominantly fast-twitch (epitrochlearis) and predominantly slow-twitch (soleus) muscles. We observed no CR-effect on phosphorylation of AS160(Ser588) or TBC1D1(Thr596), but there was a CR-induced increase in insulin-stimulated FLNc(Ser2213), GSK3α(Ser21), and GSK3β(Ser9) phosphorylation for both muscles. These results indicate that CR does not uniformly affect insulin-mediated phosphorylation of Akt substrates in fast- or slow-twitch muscles from 24 month-old rats.