INSULIN AND DIABETES CAUSE RECIPROCAL CHANGES IN THE ASSOCIATION OF EIF-4E AND PHAS-I IN RAT SKELETAL-MUSCLE

We have investigated the roles of eukaryotic initiation factor 4E (eIF -4E), the cap-binding protein, and the translational regulator, PHAS-I , in the effects of insulin and alloxan-induced diabetes on protein sy nthesis in rat skeletal muscle. Diabetes increased the amount of eIF-4 E found in the inactive PHAS-I eIF-4E complex by threefold, explaining in part the inhibitory effect of insulin deficiency on translation in itiation. Insulin treatment of diabetic rats caused dissociation of th e complex, consistent with the action of the hormone on reversing the inhibitory effect of diabetes on translation initiation. The effects o f both insulin and diabetes on PHAS-I binding to eIF-4E appeared to be due to changes in PHAS-I phosphorylation. Neither insulin nor diabete s changed the phosphorylation state of eIF-4E. The results indicate th at the effects of both insulin and diabetes on protein synthesis in sk eletal muscle involve modulation of the interaction of PHAS-I and eIF- 4E.