Effects of insulin and diabetes on the association of eukaryotic initiation factor 4e and the translational regulator, phas-i, in rat skeletal muscle
Our previous studies have shown that protein synthesis is inhibited in rat skeletal muscle during diabetes and that the inhibition is rapidly reversed by insulin treatment of diabetic rats. In the present study, we have investigated the roles of the cap-binding protein, eukaryotic initiation factor 4E (eIF-4E), and the translational regulator, PHAS-I. in the effects of insulin and alloxaninduced diabetes on protein synthesis in rat skeletal muscle. We found that diabetes increased the amount of eIF-4E present in the inactive PHAS-I-eIF-4E complex by 3-fold, explaining in part the inhibitory effect of insulin deficiency on translation initiation. Two hours after insulin treatment of diabetic rats, the amount of PHAS-I present in the PHAS-I-eIF-4E complex was reduced to control values, consistent with the action of the hormone on reversing the inhibitory effect of diabetes on translation initiation. The effects of both insulin and diabetes on PHAS-I binding to eIF-4E correlated with changes in PHAS-I phosphorylation. Neither insulin nor diabetes changed the phosphorylation state of eIF-4E. The results indicate that the effects of both insulin and diabetes on protein synthesis in skeletal muscle involve modulation of the interaction of PHAS-I and eIF-4E. Supported by NIH grants DK15658 (LSJl and DK28312 and AR41180 (JCL).
Jefferson, LS; Kimball, SR; Fadden, P; Haystead, TAJ; Lawrence, JC
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