PMID- 29439088
OWN - NLM
STAT- MEDLINE
DCOM- 20190814
LR  - 20190814
IS  - 1479-6805 (Electronic)
IS  - 0022-0795 (Linking)
VI  - 237
IP  - 1
DP  - 2018 Apr
TI  - Metabolic effects of short-term caloric restriction in mice with reduced insulin 
      gene dosage.
PG  - 59-71
LID - 10.1530/JOE-17-0505 [doi]
AB  - Caloric restriction (CR) is the only environmental intervention with robust 
      evidence that it extends lifespan and delays the symptoms of aging, but its 
      mechanisms are incompletely understood. Based on the prolonged longevity of 
      knockout models, it was hypothesized that the insulin-IGF pathway could be a 
      target for developing a CR mimic. This study aimed to test whether CR has 
      additive effects on glucose homeostasis and beta-cell function in mice with 
      reduced insulin gene dosage. To study models with a range of basal insulin 
      levels, wild-type C57BL/6J and mice on an Ins2(-)(/)(-) background, were put on 8 
      weeks of 40% CR at various ages. Both male and female mice rapidly lost weight 
      due to a reduced WAT mass. Glucose tolerance was improved and fasting glucose 
      levels were reduced by CR in both wild type and 45- and 70-week-old Ins2(-)(/)(-) 
      mice. The effects of CR and reduced insulin on glucose tolerance were 
      non-additive in 20-week-old mice. Interestingly, mice on CR generally exhibited 
      an inability to further depress blood glucose after insulin injection, pointing 
      to possible alterations in insulin sensitivity. In conclusion, our results 
      demonstrate that CR can cause weight loss in the context of reduced insulin 
      production, but that CR-improved glucose homeostasis does not occur near the 
      'insulin floor' in young mice. Collectively, these data shed further light on the 
      relationships between CR, insulin and glucose homeostasis.
CI  - (c) 2018 Society for Endocrinology.
FAU - Dommerholt, Marleen B
AU  - Dommerholt MB
AD  - Department of Cellular and Physiological SciencesUniversity of British Columbia, 
      Vancouver, Canada.
AD  - Department of PediatricsUniversity Medical Center Groningen, University of 
      Groningen, Groningen, The Netherlands.
FAU - Dionne, Derek A
AU  - Dionne DA
AD  - Department of Cellular and Physiological SciencesUniversity of British Columbia, 
      Vancouver, Canada.
FAU - Hutchinson, Daria F
AU  - Hutchinson DF
AD  - Department of Cellular and Physiological SciencesUniversity of British Columbia, 
      Vancouver, Canada.
FAU - Kruit, Janine K
AU  - Kruit JK
AD  - Department of PediatricsUniversity Medical Center Groningen, University of 
      Groningen, Groningen, The Netherlands.
FAU - Johnson, James D
AU  - Johnson JD
AD  - Department of Cellular and Physiological SciencesUniversity of British Columbia, 
      Vancouver, Canada James.D.Johnson@ubc.ca.
LA  - eng
GR  - CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180209
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
RN  - 0 (Ins1 protein, mouse)
RN  - 0 (Ins2 protein, mouse)
RN  - 0 (Insulin)
RN  - IY9XDZ35W2 (Glucose)
MH  - Adipose Tissue/growth & development/*metabolism
MH  - Animals
MH  - Caloric Restriction/*methods
MH  - Cells, Cultured
MH  - Energy Metabolism/genetics
MH  - Female
MH  - Gene Dosage/*physiology
MH  - Glucose/*metabolism/pharmacology
MH  - Insulin/*genetics/metabolism
MH  - Insulin Resistance/genetics
MH  - Islets of Langerhans/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Time Factors
MH  - Weight Loss/genetics
OTO - NOTNLM
OT  - caloric restriction
OT  - glucose homeostasis
OT  - hypoinsulinemia
OT  - insulin production
EDAT- 2018/02/14 06:00
MHDA- 2019/08/15 06:00
CRDT- 2018/02/14 06:00
PHST- 2018/01/24 00:00 [received]
PHST- 2018/02/08 00:00 [accepted]
PHST- 2018/02/14 06:00 [pubmed]
PHST- 2019/08/15 06:00 [medline]
PHST- 2018/02/14 06:00 [entrez]
AID - JOE-17-0505 [pii]
AID - 10.1530/JOE-17-0505 [doi]
PST - ppublish
SO  - J Endocrinol. 2018 Apr;237(1):59-71. doi: 10.1530/JOE-17-0505. Epub 2018 Feb 9.