Muscle fiber type specificity in insulin signal transduction

We determined the muscle fiber type-specific response of intracellular sign aling proteins to insulin. Epitrochlearis (Epi; 15% type I, 20% type IIa, a nd 65% type IIb), soleus (84, 16, and 0%), and extensor digitorum longus (E DL; 3, 57, and 40%) muscles from Wistar rats were incubated without or with 120 nM insulin (3-40 min). Peak insulin receptor (IR) tyrosine phosphoryla tion was reached after 6 (soleus) and 20 (Epi and EDL) min, with sustained activity throughout insulin exposure (40 min). Insulin increased insulin re ceptor substrate (IRS)-1 and IRS-2 tyrosine phosphorylation and phosphotyro sine-associated phosphatidylinositol (PI)-3-kinase activity to a maximal le vel after 3-10 min, with subsequent downregulation. Akt kinase phosphorylat ion peaked at 20 min, with sustained activity throughout insulin exposure. Importantly, the greatest insulin response for all signaling intermediates was observed in soleus, whereas the insulin response between EDL and Epi wa s similar. Protein expression of the p85 alpha-subunit of PI 3-kinase and A kt kinase, but not IR, IRS-1, or IRS-2, was greater in oxidative versus gly colytic muscle. In conclusion, increased function and/or expression of key proteins in the insulin-signaling cascade contribute to fiber type-specific differences in insulin action in skeletal muscle.