PMID- 21985785
OWN - NLM
STAT- MEDLINE
DCOM- 20120103
LR  - 20211020
IS  - 1558-8238 (Electronic)
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 121
IP  - 11
DP  - 2011 Nov
TI  - Sirt1 enhances skeletal muscle insulin sensitivity in mice during caloric 
      restriction.
PG  - 4281-8
LID - 58554 [pii]
LID - 10.1172/JCI58554 [doi]
AB  - Skeletal muscle insulin resistance is a key component of the etiology of type 2 
      diabetes. Caloric restriction (CR) enhances the sensitivity of skeletal muscle to 
      insulin. However, the molecular signals within skeletal muscle linking CR to 
      improved insulin action remain largely unknown. Recently, the mammalian ortholog 
      of Sir2, sirtuin 1 (Sirt1), has been identified as a potential transducer of 
      perturbations in cellular energy flux into subsequent metabolic adaptations, 
      including modulation of skeletal muscle insulin action. Here, we have 
      demonstrated that CR increases Sirt1 deacetylase activity in skeletal muscle in 
      mice, in parallel with enhanced insulin-stimulated phosphoinositide 3-kinase 
      (PI3K) signaling and glucose uptake. These adaptations in skeletal muscle insulin 
      action were completely abrogated in mice lacking Sirt1 deacetylase activity. 
      Mechanistically, Sirt1 was found to be required for the deacetylation and 
      inactivation of the transcription factor Stat3 during CR, which resulted in 
      decreased gene and protein expression of the p55alpha/p50alpha subunits of PI3K, thereby 
      promoting more efficient PI3K signaling during insulin stimulation. Thus, these 
      data demonstrate that Sirt1 is an integral signaling node in skeletal muscle 
      linking CR to improved insulin action, primarily via modulation of PI3K 
      signaling.
FAU - Schenk, Simon
AU  - Schenk S
AD  - Division of Endocrinology and Metabolism, Department of Medicine, University of 
      California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0673, USA.
FAU - McCurdy, Carrie E
AU  - McCurdy CE
FAU - Philp, Andrew
AU  - Philp A
FAU - Chen, Mark Z
AU  - Chen MZ
FAU - Holliday, Michael J
AU  - Holliday MJ
FAU - Bandyopadhyay, Gautum K
AU  - Bandyopadhyay GK
FAU - Osborn, Olivia
AU  - Osborn O
FAU - Baar, Keith
AU  - Baar K
FAU - Olefsky, Jerrold M
AU  - Olefsky JM
LA  - eng
GR  - DK033651/DK/NIDDK NIH HHS/United States
GR  - P01 DK074868/DK/NIDDK NIH HHS/United States
GR  - R24 HD050837/HD/NICHD NIH HHS/United States
GR  - U54 HD012303-25/HD/NICHD NIH HHS/United States
GR  - P30 AR058878/AR/NIAMS NIH HHS/United States
GR  - R01 DK033651/DK/NIDDK NIH HHS/United States
GR  - P30 DK063491/DK/NIDDK NIH HHS/United States
GR  - P30 AR058878-02/AR/NIAMS NIH HHS/United States
GR  - K12 HD057022/HD/NICHD NIH HHS/United States
GR  - DK063491/DK/NIDDK NIH HHS/United States
GR  - DK074868/DK/NIDDK NIH HHS/United States
GR  - UL1 RR024146/RR/NCRR NIH HHS/United States
GR  - T32 DK007494/DK/NIDDK NIH HHS/United States
GR  - U54 HD012303/HD/NICHD NIH HHS/United States
GR  - R37 DK033651/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111010
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (DNA Primers)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.5.1.- (Sirt1 protein, mouse)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - *Caloric Restriction
MH  - DNA Primers/genetics
MH  - Diabetes Mellitus, Type 2/etiology/metabolism
MH  - Glucose Clamp Technique
MH  - Insulin Resistance/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Muscle, Skeletal/*metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - Signal Transduction
MH  - Sirtuin 1/deficiency/genetics/*metabolism
PMC - PMC3204844
EDAT- 2011/10/12 06:00
MHDA- 2012/01/04 06:00
PMCR- 2011/10/10
CRDT- 2011/10/12 06:00
PHST- 2011/04/18 00:00 [received]
PHST- 2011/09/07 00:00 [accepted]
PHST- 2011/10/12 06:00 [entrez]
PHST- 2011/10/12 06:00 [pubmed]
PHST- 2012/01/04 06:00 [medline]
PHST- 2011/10/10 00:00 [pmc-release]
AID - 58554 [pii]
AID - 10.1172/JCI58554 [doi]
PST - ppublish
SO  - J Clin Invest. 2011 Nov;121(11):4281-8. doi: 10.1172/JCI58554. Epub 2011 Oct 10.