PMID- 23648089
OWN - NLM
STAT- MEDLINE
DCOM- 20131216
LR  - 20221207
IS  - 1474-9726 (Electronic)
IS  - 1474-9718 (Print)
IS  - 1474-9718 (Linking)
VI  - 12
IP  - 4
DP  - 2013 Aug
TI  - Young and old genetically heterogeneous HET3 mice on a rapamycin diet are glucose 
      intolerant but insulin sensitive.
PG  - 712-8
LID - 10.1111/acel.12097 [doi]
AB  - Rapamycin, an inhibitor of the mechanistic target of rapamycin (mTOR) signaling 
      pathway, extends the life span of yeast, worms, flies, and mice. Interventions 
      that promote longevity are often correlated with increased insulin sensitivity, 
      and it therefore is surprising that chronic rapamycin treatment of mice, rats, 
      and humans is associated with insulin resistance (J Am Soc Nephrol., 19, 2008, 
      1411; Diabetes, 00, 2010, 00; Science, 335, 2012, 1638). We examined the effect 
      of dietary rapamycin treatment on glucose homeostasis and insulin resistance in 
      the genetically heterogeneous HET3 mouse strain, a strain in which dietary 
      rapamycin robustly extends mean and maximum life span. We find that rapamycin 
      treatment leads to glucose intolerance in both young and old HET3 mice, but in 
      contrast to the previously reported effect of injected rapamycin in C57BL/6 mice, 
      HET3 mice treated with dietary rapamycin responded normally in an insulin 
      tolerance test. To gauge the overall consequences of rapamycin treatment on 
      average blood glucose levels, we measured HBA1c. Dietary rapamycin increased 
      HBA1c over the first 3 weeks of treatment in young animals, but the effect was 
      lost by 3 months, and no effect was detected in older animals. Our results 
      demonstrate that the extended life span of HET3 mice on a rapamycin diet occurs 
      in the absence of major changes in insulin sensitivity and highlight the 
      importance of strain background and delivery method in testing effects of 
      longevity interventions.
CI  - (c) 2013 John Wiley & Sons Ltd and the Anatomical Society.
FAU - Lamming, Dudley W
AU  - Lamming DW
AD  - Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
FAU - Ye, Lan
AU  - Ye L
FAU - Astle, Clinton M
AU  - Astle CM
FAU - Baur, Joseph A
AU  - Baur JA
FAU - Sabatini, David M
AU  - Sabatini DM
FAU - Harrison, David E
AU  - Harrison DE
LA  - eng
GR  - R01 CA103866/CA/NCI NIH HHS/United States
GR  - AG 022308/AG/NIA NIH HHS/United States
GR  - CA 129105/CA/NCI NIH HHS/United States
GR  - 1K99AG041765-01A1/AG/NIA NIH HHS/United States
GR  - AG 035860/AG/NIA NIH HHS/United States
GR  - R01 AG038560/AG/NIA NIH HHS/United States
GR  - R01 CA129105/CA/NCI NIH HHS/United States
GR  - P30 DK019525/DK/NIDDK NIH HHS/United States
GR  - U01 AG022308/AG/NIA NIH HHS/United States
GR  - R01 AG043483/AG/NIA NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - P30 CA034196/CA/NCI NIH HHS/United States
GR  - P30DK19525/DK/NIDDK NIH HHS/United States
GR  - K99 AG041765/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130607
PL  - England
TA  - Aging Cell
JT  - Aging cell
JID - 101130839
RN  - 0 (Blood Glucose)
RN  - 0 (Glycated Hemoglobin A)
RN  - 8558G7RUTR (Pyruvic Acid)
RN  - IY9XDZ35W2 (Glucose)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - Blood Glucose
MH  - Diet
MH  - Female
MH  - *Genetic Heterogeneity
MH  - Genotype
MH  - Glucose/metabolism
MH  - *Glucose Intolerance
MH  - Glycated Hemoglobin/analysis
MH  - *Insulin Resistance
MH  - Longevity
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pyruvic Acid/metabolism
MH  - Sirolimus/*administration & dosage/pharmacology
MH  - Species Specificity
PMC - PMC3727050
MID - NIHMS475453
OTO - NOTNLM
OT  - aging
OT  - glucose tolerance
OT  - heterogeneous mice
OT  - insulin tolerance
OT  - rapamycin
EDAT- 2013/05/08 06:00
MHDA- 2013/12/18 06:00
PMCR- 2014/08/01
CRDT- 2013/05/08 06:00
PHST- 2013/04/24 00:00 [accepted]
PHST- 2013/05/08 06:00 [entrez]
PHST- 2013/05/08 06:00 [pubmed]
PHST- 2013/12/18 06:00 [medline]
PHST- 2014/08/01 00:00 [pmc-release]
AID - 10.1111/acel.12097 [doi]
PST - ppublish
SO  - Aging Cell. 2013 Aug;12(4):712-8. doi: 10.1111/acel.12097. Epub 2013 Jun 7.