Low- and high-protein diets do not alter ex vivo insulin action in skeletal muscle

A low-protein high carbohydrate (LPHC) diet and a high-protein low carbohydrate (HPLC) diet have been reported to positively and negatively regulate whole-body glucose tolerance and insulin sensitivity, respectively. Skeletal muscle is quantitatively the most important tissue clearing glucose in the postprandial state, but it is unclear if LPHC and HPLC diets directly influence insulin action in skeletal muscle. To test this, mice were placed on control chow diet, LPHC and HPLC diets for 13.5 weeks at which time the submaximal insulin-stimulated glucose transport and insulin signaling were evaluated in ex vivo incubated oxidative soleus and glycolytic EDL muscle. At the whole-body level, the diets had the anticipated effects, with LPHC diet improving glucose tolerance and insulin-sensitivity whereas HPLC diet had the opposite effect. However, neither insulin-stimulated Akt/TBC1D4 signaling and glucose transport ex vivo, nor cell signaling in vivo were altered by the diets. These data imply that skeletal muscle insulin sensitivity does not contribute to the whole-body effects of LPHC and HPLC diets on glucose metabolism.