Insulin and diabetes cause reciprocal changes in the association of
eukaryotic initiation factor 4e and the translational regulator,
phas-i, in rat skeletal muscle.
Kimball, Scot R., Leonard S. Jefferson, Patrick Fadden, Timothy A. J.
Haystead, and John C. Lawrence, Jr.
Department of Cellular and Molecular Physiology, The Pennsylvania
State University, College of Medicine, Hershey, PA 17033, Department
of Pharmacology, University of Virginia School of Medicine,
Charlottesville, VA 22903, Department of Molecular Biology and
Pharmacology, Washington University School of Medicine, St. Louis, MO
63110
APStracts 2:0406C, 1995.
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 synthesis in rat skeletal muscle. Diabetes increased the
amount of eIF-4E found in the inactive PHAS-I x eIF-4E complex by 3
-fold, explaining in part the inhibitory effect of insulin deficiency
on translation initiation. Insulin treatment of diabetic rats caused
dissociation of the complex, 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 appeared to be due to 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.
Received 25 September 1995; accepted in final form 8 November
1995.
APS Manuscript Number C582-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95