PMID- 33132310
OWN - NLM
STAT- MEDLINE
DCOM- 20210716
LR  - 20210716
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 43
IP  - 11
DP  - 2020
TI  - LRRK2 Inhibition Ameliorates Dexamethasone-Induced Glucose Intolerance via 
      Prevents Impairment in GLUT4 Membrane Translocation in Adipocytes.
PG  - 1660-1668
LID - 10.1248/bpb.b20-00377 [doi]
AB  - Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are associated with 
      Parkinson's disease. LRRK2 is a large protein with multiple functional domains, 
      including a guanosine 5'-triphosphate (GTP)-binding domain and a protein kinase 
      domain. Recent studies indicated that the members of the Rab GTPase family, Rab8a 
      and Rab10, which are involved in the membrane transport of the glucose 
      transporter type 4 (GLUT4) during insulin-dependent glucose uptake, are 
      phosphorylated by LRRK2. However, the physiological role of LRRK2 in the 
      regulation of glucose metabolism is largely unknown. In the present study, we 
      investigated the role of LRRK2 using dexamethasone (DEX)-induced glucose 
      intolerance in mice. LRRK2 knockout (KO) mice exhibited suppressed glucose 
      intolerance, even after treatment with DEX. The phosphorylation of LRRK2, Rab8a 
      and Rab10 was increased in the adipose tissues of DEX-treated wild-type mice. In 
      addition, inhibition of the LRRK2 kinase activity prevented the DEX-induced 
      inhibition of GLUT4 membrane translocation and glucose uptake in cultured 3T3-L1 
      adipocytes. These results suggest that LRRK2 plays an important role in glucose 
      metabolism in adipose tissues.
FAU - Imai, Motoki
AU  - Imai M
AD  - Department of Regulation Biochemistry, Graduate School of Medical Sciences, 
      Kitasato University.
FAU - Kawakami, Fumitaka
AU  - Kawakami F
AD  - Department of Regulation Biochemistry, Graduate School of Medical Sciences, 
      Kitasato University.
AD  - Research Facility of Regenerative Medicine and Cell Design, Kitasato University 
      School of Allied Health Science.
FAU - Kubo, Makoto
AU  - Kubo M
AD  - Research Facility of Regenerative Medicine and Cell Design, Kitasato University 
      School of Allied Health Science.
AD  - Division of Clinical Immunology, Graduate School of Medical Sciences, Kitasato 
      University.
FAU - Kanzaki, Makoto
AU  - Kanzaki M
AD  - Department of Biomedical Engineering, Graduate School of Biomedical Engineering, 
      Tohoku University.
FAU - Maruyama, Hiroko
AU  - Maruyama H
AD  - Research Facility of Regenerative Medicine and Cell Design, Kitasato University 
      School of Allied Health Science.
AD  - Department of Cytopathology, Graduate School of Medical Sciences, Kitasato 
      University.
FAU - Kawashima, Rei
AU  - Kawashima R
AD  - Department of Regulation Biochemistry, Graduate School of Medical Sciences, 
      Kitasato University.
AD  - Research Facility of Regenerative Medicine and Cell Design, Kitasato University 
      School of Allied Health Science.
FAU - Maekawa, Tatsunori
AU  - Maekawa T
AD  - Department of Regulation Biochemistry, Graduate School of Medical Sciences, 
      Kitasato University.
AD  - Research Facility of Regenerative Medicine and Cell Design, Kitasato University 
      School of Allied Health Science.
FAU - Kurosaki, Yoshifumi
AU  - Kurosaki Y
AD  - Research Facility of Regenerative Medicine and Cell Design, Kitasato University 
      School of Allied Health Science.
AD  - Department of Medical Laboratory Sciences, Kitasato University School of Allied 
      Health Sciences.
FAU - Kojima, Fumiaki
AU  - Kojima F
AD  - Research Facility of Regenerative Medicine and Cell Design, Kitasato University 
      School of Allied Health Science.
AD  - Department of Pharmacology, Kitasato University School of Allied Health Sciences.
FAU - Ichikawa, Takafumi
AU  - Ichikawa T
AD  - Department of Regulation Biochemistry, Graduate School of Medical Sciences, 
      Kitasato University.
AD  - Research Facility of Regenerative Medicine and Cell Design, Kitasato University 
      School of Allied Health Science.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Glucose Transporter Type 4)
RN  - 0 (Slc2a4 protein, mouse)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 2.7.11.1 (Leucine-Rich Repeat Serine-Threonine Protein Kinase-2)
RN  - EC 2.7.11.1 (Lrrk2 protein, mouse)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/cytology/drug effects/metabolism
MH  - Adipose Tissue/cytology/drug effects/*metabolism
MH  - Animals
MH  - Cell Membrane/drug effects/metabolism
MH  - Dexamethasone/*adverse effects
MH  - Disease Models, Animal
MH  - Glucose/metabolism
MH  - Glucose Intolerance/chemically induced/*pathology
MH  - Glucose Transporter Type 4/*metabolism
MH  - Humans
MH  - Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Phosphorylation/drug effects
OTO - NOTNLM
OT  - adipocyte
OT  - dexamethasone
OT  - glucose intolerance
OT  - glucose transporter 4 (GLUT4)
OT  - leucine-rich repeat kinase 2 (LRRK2)
EDAT- 2020/11/03 06:00
MHDA- 2021/07/17 06:00
CRDT- 2020/11/02 06:11
PHST- 2020/11/02 06:11 [entrez]
PHST- 2020/11/03 06:00 [pubmed]
PHST- 2021/07/17 06:00 [medline]
AID - 10.1248/bpb.b20-00377 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2020;43(11):1660-1668. doi: 10.1248/bpb.b20-00377.