PMID- 12837665
OWN - NLM
STAT- MEDLINE
DCOM- 20031030
LR  - 20151119
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 285
IP  - 4
DP  - 2003 Oct
TI  - Tissue-specific regulation of protein synthesis by insulin and free fatty acids.
PG  - E754-62
AB  - 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.
FAU - Crozier, Stephen J
AU  - Crozier SJ
AD  - Department of Cellular and Molecular Physiology, The Pennsylvania State 
      University College of Medicine, Hershey, PA 17033, USA.
FAU - Anthony, Joshua C
AU  - Anthony JC
FAU - Schworer, Charles M
AU  - Schworer CM
FAU - Reiter, Ali K
AU  - Reiter AK
FAU - Anthony, Tracy G
AU  - Anthony TG
FAU - Kimball, Scot R
AU  - Kimball SR
FAU - Jefferson, Leonard S
AU  - Jefferson LS
LA  - eng
GR  - DK 15658/DK/NIDDK NIH HHS/United States
GR  - GM 08619/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030701
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Eukaryotic Initiation Factor-2B)
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Insulin)
RN  - 2679MF687A (Niacin)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Experimental/chemically induced/metabolism
MH  - Eukaryotic Initiation Factor-2B/*metabolism
MH  - Fatty Acids, Nonesterified/*metabolism
MH  - Heart/drug effects
MH  - Insulin/*metabolism
MH  - Male
MH  - Muscle, Skeletal/drug effects/*metabolism
MH  - Myocardium/*metabolism
MH  - Niacin/pharmacology
MH  - Organ Specificity
MH  - *Protein Biosynthesis
MH  - Protein Processing, Post-Translational
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sirolimus/*metabolism
EDAT- 2003/07/03 05:00
MHDA- 2003/10/31 05:00
CRDT- 2003/07/03 05:00
PHST- 2003/07/03 05:00 [pubmed]
PHST- 2003/10/31 05:00 [medline]
PHST- 2003/07/03 05:00 [entrez]
AID - 00063.2003 [pii]
AID - 10.1152/ajpendo.00063.2003 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2003 Oct;285(4):E754-62. doi: 
      10.1152/ajpendo.00063.2003. Epub 2003 Jul 1.