Leukemia inhibitory factor stimulates muscle glucose uptake by a PI3-kinase dependent pathway that is maintained in white muscle in obesity (1162.4)

OBJECTIVE: To investigates the metabolic effects of leukemia inhibitory factor (LIF) in mouse skeletal muscle. METHODS: Effects of LIF on muscle glucose transport, palmitate oxidation and cellular signaling were investigated in soleus and extensor digitorum longus (EDL) muscles from chow and highfat diet fed wildtype (WT) mice or chow fed muscle-specific AMPKα2 kinase-dead (KD) and suppressors of cytokine signaling (SOCS) 3 muscle-specific knockout mice. RESULTS: LIF increased muscle glucose transport in a dose- and time-dependent manner. LIF increased Akt Ser473-P, whereas AMPK Thr172-P was unaffected. Incubation of muscles from KD or WT mice with Wortmannin, LY294002 and Parthenolide demonstrated that PI3-kinase, but not AMPK, was essential for LIF-stimulated glucose transport. Incubation with Rapamycin and AZD8055 demonstrated that mammalian target of rapamycin complex (mTORC)2 and not mTORC1 is necessary for LIF-stimulated glucose transport. LIF-stimulated glucose transport was maintained in EDL muscl...