PMID- 16253633
OWN - NLM
STAT- MEDLINE
DCOM- 20051228
LR  - 20131121
IS  - 0026-0495 (Print)
IS  - 0026-0495 (Linking)
VI  - 54
IP  - 11
DP  - 2005 Nov
TI  - Elevated glucose activates protein synthesis in cultured cardiac myocytes.
PG  - 1453-60
AB  - Diabetes mellitus results in chronic hyperglycemia, a serious metabolic disorder 
      associated with a markedly increased risk of cardiovascular disease. However, the 
      effects of high glucose (HG) on cardiac myocyte growth have not been fully 
      clarified. In this study, the effect of glucose on cardiac myocyte growth was 
      examined using leucine incorporation as an index of protein synthesis. High 
      glucose (HG, 25 mmol/L) increased leucine incorporation (167% +/- 0.2% over 
      normal glucose, n=4, P<.01) compared with a physiological glucose concentration 
      (5.5 mmol/L, normal glucose). The HG-induced increase in leucine incorporation 
      was time- and dose-dependent and was not due to osmotic changes because 25 mmol/L 
      mannitol did not change leucine incorporation. High glucose also significantly 
      reduced elongation factor 2 phosphorylation, an effect known to result in 
      increased protein synthesis at the elongation step. Western blot analysis showed 
      that HG-activated protein kinase B (PKB), also called Akt (PKB/Akt), at 18 hours. 
      High glucose-induced leucine incorporation was attenuated with 
      phosphatidylinositol 3-kinase (PI3K) inhibition using wortmannin and LY294002 and 
      by rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, 72%, 64%, and 65% 
      (P<.05), respectively. High glucose also activated extracellular signal-regulated 
      kinase 1/2 activity with peak stimulation at 5 minutes. In addition, PD98059, an 
      inhibitor of mitogen-activated protein kinase kinase, attenuated HG-induced 
      leucine incorporation. These data show for the first time that elevated glucose 
      increases protein synthesis in cardiac myocytes. The increase appears to be 
      mediated by activation of PI3K-PKB/Akt and/or PI3K-mTOR as well as extracellular 
      signal-regulated kinase 1/2. These results provide new evidence for a direct 
      effect of glucose independent of insulin on cardiac myocyte growth.
FAU - Yeshao, Wen
AU  - Yeshao W
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      University of Virginia Health Science Center, Charlottesville, VA 22908, USA. 
      yw4w@virginia.edu
FAU - Gu, Jiali
AU  - Gu J
FAU - Peng, Xianghong
AU  - Peng X
FAU - Nairn, Angus C
AU  - Nairn AC
FAU - Nadler, Jerry L
AU  - Nadler JL
LA  - eng
GR  - P01 HL 557898/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Peptide Elongation Factor 2)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - GMW67QNF9C (Leucine)
RN  - IY9XDZ35W2 (Glucose)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Antibiotics, Antineoplastic/pharmacology
MH  - Cells, Cultured
MH  - Glucose/*pharmacology
MH  - Leucine/pharmacokinetics
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Myocytes, Cardiac/cytology/*drug effects/*metabolism
MH  - Peptide Elongation Factor 2/metabolism
MH  - Phosphorylation
MH  - Protein Biosynthesis/*drug effects/*physiology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Signal Transduction/physiology
MH  - Sirolimus/pharmacology
EDAT- 2005/10/29 09:00
MHDA- 2005/12/29 09:00
CRDT- 2005/10/29 09:00
PHST- 2004/11/16 00:00 [received]
PHST- 2005/05/08 00:00 [accepted]
PHST- 2005/10/29 09:00 [pubmed]
PHST- 2005/12/29 09:00 [medline]
PHST- 2005/10/29 09:00 [entrez]
AID - S0026-0495(05)00218-0 [pii]
AID - 10.1016/j.metabol.2005.05.010 [doi]
PST - ppublish
SO  - Metabolism. 2005 Nov;54(11):1453-60. doi: 10.1016/j.metabol.2005.05.010.