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Am J Physiol Endocrinol Metab 285: E754-E762, 2003. First published July 1, 2003; doi:10.1152/ajpendo.00063.2003
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Tissue-specific regulation of protein synthesis by insulin and free fatty acids

Stephen J. Crozier, Joshua C. Anthony, Charles M. Schworer, Ali K. Reiter, Tracy G. Anthony, Scot R. Kimball, and Leonard S. Jefferson

Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey Pennsylvania 17033

Submitted 12 February 2003 ; accepted in final form 7 May 2003

The purpose of the study described herein was to investigate how the mammalian target of rapamycin (mTOR)-signaling pathway and eukaryotic initiation factor 2B (eIF2B) activity, both having key roles in the translational control of protein synthesis in skeletal muscle, are regulated in cardiac muscle of rats in response to two different models of altered free fatty acid (FFA) and insulin availability. Protein synthetic rates were reduced in both gastrocnemius and heart of 3-day diabetic rats. The reduction was associated with diminished mTOR-mediated signaling and eIF2B activity in the gastrocnemius but only with diminished mTOR signaling in the heart. In response to the combination of acute hypoinsulinemia and hypolipidemia induced by administration of niacin, protein synthetic rates were also diminished in both gastrocnemius and heart. The niacin-induced changes were associated with diminished mTOR signaling and eIF2B activity in the heart but only with decreased mTOR signaling in the gastrocnemius. In the heart, mTOR signaling and eIF2B activity correlated with cellular energy status and/or redox potential. Thus FFAs may contribute to the translational control of protein synthesis in the heart but not in the gastrocnemius. In contrast, insulin, but not FFAs, is required for the maintenance of protein synthesis in the gastrocnemius.

translation initiation; energy status; AMP-activated protein kinase; pyridine dinucleotides


Address for reprint requests and other correspondence: L. S. Jefferson, Dept. of Cellular and Molecular Physiology, The Pennsylvania State Univ. College of Medicine, PO Box 850, Hershey, PA 17033 (E-mail: jjefferson{at}psu.edu).




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 Am. J. Physiol. Heart Circ. Physiol.Home page
S. J. Crozier, T. C. Vary, S. R. Kimball, and L. S. Jefferson
Cellular energy status modulates translational control mechanisms in ischemic-reperfused rat hearts
Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1242 - H1250.
[Abstract] [Full Text] [PDF]


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