Inactivity causes
insulin resistance in skeletal muscle and exacerbates various lifestyle-related diseases. We previously found that 24-h hindlimb cast immobilization (HCI) of the predominantly slow-twitch soleus muscle increased intramyocellular
diacylglycerol (IMDG) and
insulin resistance by activation of lipin1, and HCI after a high-fat diet (HFD) further aggravated
insulin resistance. Here, we investigated the effects of HCI on the fast-twitch-predominant plantaris muscle. HCI reduced the
insulin sensitivity of plantaris muscle by approximately 30%, and HCI following HFD dramatically reduced
insulin sensitivity by approximately 70% without significant changes in the amount of IMDG.
Insulin-stimulated phosphorylation levels of
insulin receptor (IR), IR substrate-1, and Akt were reduced in parallel with the decrease in
insulin sensitivity. Furthermore,
tyrosine phosphatase 1B (PTP1B), a
protein known to inhibit
insulin action by dephosphorylating IR, was activated, and PTP1B inhibition canceled HCI-induced
insulin resistance. In conclusion, HCI causes
insulin resistance in the fast-twitch-predominant plantaris muscle as well as in the slow-twitch-predominant soleus muscle, and HFD potentiates these effects in both muscle types. However, the mechanism differed between soleus and plantaris muscles, since
insulin resistance was mediated by the PTP1B inhibition at IR in plantaris muscle.