PMID- 31003779
OWN - NLM
STAT- MEDLINE
DCOM- 20200710
LR  - 20200710
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 513
IP  - 4
DP  - 2019 Jun 11
TI  - Inhibition of GIP signaling extends lifespan without caloric restriction.
PG  - 974-982
LID - S0006-291X(19)30658-8 [pii]
LID - 10.1016/j.bbrc.2019.04.036 [doi]
AB  - AIMS/INTRODUCTION: Caloric restriction (CR) promotes longevity and exerts 
      anti-aging effects by increasing Sirtuin production and activation. Gastric 
      inhibitory polypeptide (GIP), a gastrointestinal peptide hormone, exerts various 
      effects on pancreatic beta-cells and extra-pancreatic tissues. GIP promotes 
      glucose-dependent augmentation of insulin secretion and uptake of nutrients into 
      the adipose tissue. MATERIALS AND METHODS: Gipr(-/-) and Gipr(+/+) mice were used 
      for lifespan analysis, behavior experiments and gene expression of adipose tissue 
      and muscles. 3T3-L1 differentiated adipocytes were used for Sirt1 and Nampt 
      expression followed by treatment with GIP and alpha-lipoic acid. RESULTS: We observed 
      that GIP receptor-knockout (Gipr(-/-)) mice fed normal diet showed an extended 
      lifespan, increased exploratory and decreased anxiety-based behaviors, which are 
      characteristic behavioral changes under CR. Moreover, Gipr(-/-) mice showed 
      increased Sirt1 and Nampt expression in the adipose tissue. GIP suppressed 
      alpha-lipoic acid-induced Sirt1 expression and activity in differentiated adipocytes. 
      CONCLUSIONS: Although maintenance of CR is difficult, food intake and muscle 
      endurance of Gipr(-/-) mice were similar to those of wild-type mice. Inhibition 
      of GIP signaling may be a novel strategy to extend the lifespan of diabetic 
      patients.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Hoizumi, Manabu
AU  - Hoizumi M
AD  - Department of Endocrinology, Diabetes and Geriatric Medicine, Akita University 
      Graduate School of Medicine, Japan.
FAU - Sato, Takehiro
AU  - Sato T
AD  - Department of Endocrinology, Diabetes and Geriatric Medicine, Akita University 
      Graduate School of Medicine, Japan.
FAU - Shimizu, Tatsunori
AU  - Shimizu T
AD  - Department of Endocrinology, Diabetes and Geriatric Medicine, Akita University 
      Graduate School of Medicine, Japan.
FAU - Kato, Shunsuke
AU  - Kato S
AD  - Department of Endocrinology, Diabetes and Geriatric Medicine, Akita University 
      Graduate School of Medicine, Japan.
FAU - Tsukiyama, Katsushi
AU  - Tsukiyama K
AD  - Department of Endocrinology, Diabetes and Geriatric Medicine, Akita University 
      Graduate School of Medicine, Japan.
FAU - Narita, Takuma
AU  - Narita T
AD  - Department of Endocrinology, Diabetes and Geriatric Medicine, Akita University 
      Graduate School of Medicine, Japan.
FAU - Fujita, Hiroki
AU  - Fujita H
AD  - Department of Endocrinology, Diabetes and Geriatric Medicine, Akita University 
      Graduate School of Medicine, Japan.
FAU - Morii, Tsukasa
AU  - Morii T
AD  - Department of Endocrinology, Diabetes and Geriatric Medicine, Akita University 
      Graduate School of Medicine, Japan.
FAU - Sassa, Mariko Harada
AU  - Sassa MH
AD  - Institute for Advancement of Clinical and Translational Science, Kyoto University 
      Hospital, Japan.
FAU - Seino, Yutaka
AU  - Seino Y
AD  - Kansai Electric Power Medical Research Institute, Osaka, Japan.
FAU - Yamada, Yuichiro
AU  - Yamada Y
AD  - Department of Endocrinology, Diabetes and Geriatric Medicine, Akita University 
      Graduate School of Medicine, Japan. Electronic address: 
      yamada@gipc.akita-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190417
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Cytokines)
RN  - 0 (Receptors, Gastrointestinal Hormone)
RN  - 59392-49-3 (Gastric Inhibitory Polypeptide)
RN  - D6H00MV7K8 (gastric inhibitory polypeptide receptor)
RN  - EC 2.4.2.12 (Nicotinamide Phosphoribosyltransferase)
RN  - EC 2.4.2.12 (nicotinamide phosphoribosyltransferase, mouse)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/metabolism
MH  - Adipose Tissue/metabolism
MH  - Animals
MH  - *Caloric Restriction
MH  - Cytokines/metabolism
MH  - Gastric Inhibitory Polypeptide/*antagonists & inhibitors
MH  - Longevity/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Nicotinamide Phosphoribosyltransferase/metabolism
MH  - Receptors, Gastrointestinal Hormone/genetics
MH  - Signal Transduction/*physiology
MH  - Sirtuin 1/metabolism
OTO - NOTNLM
OT  - Adipose tissue
OT  - Gene expression
OT  - Mouse
EDAT- 2019/04/21 06:00
MHDA- 2020/07/11 06:00
CRDT- 2019/04/21 06:00
PHST- 2019/03/27 00:00 [received]
PHST- 2019/04/04 00:00 [accepted]
PHST- 2019/04/21 06:00 [pubmed]
PHST- 2020/07/11 06:00 [medline]
PHST- 2019/04/21 06:00 [entrez]
AID - S0006-291X(19)30658-8 [pii]
AID - 10.1016/j.bbrc.2019.04.036 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2019 Jun 11;513(4):974-982. doi: 
      10.1016/j.bbrc.2019.04.036. Epub 2019 Apr 17.