PMID- 19336678
OWN - NLM
STAT- MEDLINE
DCOM- 20090729
LR  - 20211020
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 58
IP  - 7
DP  - 2009 Jul
TI  - Modulation of skeletal muscle insulin signaling with chronic caloric restriction 
      in cynomolgus monkeys.
PG  - 1488-98
LID - 10.2337/db08-0977 [doi]
AB  - OBJECTIVE: Caloric restriction (CR) has been shown to retard aging processes, 
      extend maximal life span, and consistently increase insulin action in 
      experimental animals. The mechanism by which CR enhances insulin action, 
      specifically in higher species, is not precisely known. We sought to examine 
      insulin receptor signaling and transcriptional alterations in skeletal muscle of 
      nonhuman primates subjected to CR over a 4-year period. RESEARCH DESIGN AND 
      METHODS: At baseline, 32 male adult cynomolgus monkeys (Macaca fascicularis) were 
      randomized to an ad libitum (AL) diet or to 30% CR. Dietary intake, body weight, 
      and insulin sensitivity were obtained at routine intervals over 4 years. At the 
      end of the study, hyperinsulinemic-euglycemic clamps were performed and skeletal 
      muscle (vastus lateralis) was obtained in the basal and insulin-stimulated states 
      for insulin receptor signaling and gene expression profiling. RESULTS: CR 
      significantly increased whole-body insulin-mediated glucose disposal compared 
      with AL diet and increased insulin receptor signaling, i.e., insulin receptor 
      substrate (IRS)-1, insulin receptor phosphorylation, and IRS-associated PI 
      3-kinase activity in skeletal muscle (P < 0.01, P < 0.01, and P < 0.01, 
      respectively). Gene expression for insulin signaling proteins, i.e., IRS-1 and 
      IRS-2, were not increased with CR, although a significant increase in protein 
      abundance was noted. Components of the ubiquitin-proteasome system, i.e., 20S and 
      19S proteasome subunit abundance and 20S proteasome activity, were significantly 
      decreased by CR. CONCLUSIONS: CR increases insulin sensitivity on a whole-body 
      level and enhances insulin receptor signaling in this higher species. CR in 
      cynomolgus monkeys may alter insulin signaling in vivo by modulating protein 
      content of insulin receptor signaling proteins.
FAU - Wang, Zhong Q
AU  - Wang ZQ
AD  - Division of Nutrition and Chronic Diseases, Pennington Biomedical Research 
      Center, Louisiana State University System, Baton Rouge, LA, USA.
FAU - Floyd, Z Elizabeth
AU  - Floyd ZE
FAU - Qin, Jianhua
AU  - Qin J
FAU - Liu, Xiaotuan
AU  - Liu X
FAU - Yu, Yongmei
AU  - Yu Y
FAU - Zhang, Xian H
AU  - Zhang XH
FAU - Wagner, Janice D
AU  - Wagner JD
FAU - Cefalu, William T
AU  - Cefalu WT
LA  - eng
GR  - AG010816/AG/NIA NIH HHS/United States
GR  - P20 RR021945/RR/NCRR NIH HHS/United States
GR  - P30 DK072476/DK/NIDDK NIH HHS/United States
GR  - 1 P30-DK072476/DK/NIDDK NIH HHS/United States
GR  - P20-RR021945/RR/NCRR NIH HHS/United States
GR  - AG000578/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090331
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 63231-63-0 (RNA)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - *Caloric Restriction
MH  - Gene Expression Regulation
MH  - Genome, Human
MH  - Glucose/metabolism
MH  - Insulin/*physiology
MH  - Insulin Receptor Substrate Proteins/metabolism
MH  - Macaca fascicularis/*physiology
MH  - Male
MH  - Muscle, Skeletal/enzymology/*physiology
MH  - Oligonucleotide Array Sequence Analysis
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA/genetics/isolation & purification
MH  - Receptor, Insulin/metabolism/physiology
MH  - Signal Transduction/*physiology
PMC - PMC2699875
EDAT- 2009/04/02 09:00
MHDA- 2009/07/30 09:00
PMCR- 2010/07/01
CRDT- 2009/04/02 09:00
PHST- 2009/04/02 09:00 [entrez]
PHST- 2009/04/02 09:00 [pubmed]
PHST- 2009/07/30 09:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - db08-0977 [pii]
AID - 0977 [pii]
AID - 10.2337/db08-0977 [doi]
PST - ppublish
SO  - Diabetes. 2009 Jul;58(7):1488-98. doi: 10.2337/db08-0977. Epub 2009 Mar 31.