PMID- 34876563
OWN - NLM
STAT- MEDLINE
DCOM- 20220408
LR  - 20231108
IS  - 2041-4889 (Electronic)
VI  - 12
IP  - 12
DP  - 2021 Dec 7
TI  - Underlying mechanisms of glucocorticoid-induced beta-cell death and dysfunction: a 
      new role for glycogen synthase kinase 3.
PG  - 1136
LID - 10.1038/s41419-021-04419-8 [doi]
LID - 1136
AB  - Glucocorticoids (GCs) are widely prescribed for their anti-inflammatory and 
      immunosuppressive properties as a treatment for a variety of diseases. The use of 
      GCs is associated with important side effects, including diabetogenic effects. 
      However, the underlying mechanisms of GC-mediated diabetogenic effects in beta-cells 
      are not well understood. In this study we investigated the role of glycogen 
      synthase kinase 3 (GSK3) in the mediation of beta-cell death and dysfunction induced 
      by GCs. Using genetic and pharmacological approaches we showed that GSK3 is 
      involved in GC-induced beta-cell death and impaired insulin secretion. Further, we 
      unraveled the underlying mechanisms of GC-GSK3 crosstalk. We showed that GSK3 is 
      marginally implicated in the nuclear localization of GC receptor (GR) upon ligand 
      binding. Furthermore, we showed that GSK3 regulates the expression of GR at mRNA 
      and protein levels. Finally, we dissected the proper contribution of each GSK3 
      isoform and showed that GSK3beta isoform is sufficient to mediate the pro-apoptotic 
      effects of GCs in beta-cells. Collectively, in this work we identified GSK3 as a 
      viable target to mitigate GC deleterious effects in pancreatic beta-cells.
CI  - (c) 2021. The Author(s).
FAU - Delangre, Etienne
AU  - Delangre E
AD  - Universite de Paris, BFA, UMR 8251, CNRS, Team << Biologie et Pathologie du 
      Pancreas Endocrine >>, Paris, France.
FAU - Liu, Junjun
AU  - Liu J
AD  - Universite de Paris, BFA, UMR 8251, CNRS, Team << Biologie et Pathologie du 
      Pancreas Endocrine >>, Paris, France.
AD  - Shandong Institute of Endocrine & Metabolic Diseases, Shandong First Medical 
      University & Shandong Academy of Medical Sciences, Jinan, China.
FAU - Tolu, Stefania
AU  - Tolu S
AD  - Universite de Paris, BFA, UMR 8251, CNRS, Team << Biologie et Pathologie du 
      Pancreas Endocrine >>, Paris, France.
FAU - Maouche, Kamel
AU  - Maouche K
AD  - Universite de Paris, BFA, UMR 8251, CNRS, Team << Biologie et Pathologie du 
      Pancreas Endocrine >>, Paris, France.
FAU - Armanet, Mathieu
AU  - Armanet M
AD  - Cell Therapy Unit, Saint-Louis hospital, AP-HP, and Universite de Paris, Paris, 
      France.
FAU - Cattan, Pierre
AU  - Cattan P
AD  - Cell Therapy Unit, Saint-Louis hospital, AP-HP, and Universite de Paris, Paris, 
      France.
FAU - Pommier, Gaelle
AU  - Pommier G
AD  - Universite de Paris, BFA, UMR 8251, CNRS, Team << Biologie et Pathologie du 
      Pancreas Endocrine >>, Paris, France.
FAU - Bailbe, Danielle
AU  - Bailbe D
AD  - Universite de Paris, BFA, UMR 8251, CNRS, Team << Biologie et Pathologie du 
      Pancreas Endocrine >>, Paris, France.
FAU - Movassat, Jamileh
AU  - Movassat J
AUID- ORCID: 0000-0002-0314-1525
AD  - Universite de Paris, BFA, UMR 8251, CNRS, Team << Biologie et Pathologie du 
      Pancreas Endocrine >>, Paris, France. jamileh.movassat@u-paris.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211207
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Glucocorticoids)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Apoptosis
MH  - Cell Death
MH  - *Glucocorticoids/adverse effects
MH  - *Glycogen Synthase Kinase 3/genetics
MH  - Glycogen Synthase Kinase 3 beta/genetics
PMC - PMC8651641
COIS- The authors declare no competing interests.
EDAT- 2021/12/09 06:00
MHDA- 2022/04/09 06:00
PMCR- 2021/12/07
CRDT- 2021/12/08 05:55
PHST- 2021/06/22 00:00 [received]
PHST- 2021/11/18 00:00 [accepted]
PHST- 2021/11/10 00:00 [revised]
PHST- 2021/12/08 05:55 [entrez]
PHST- 2021/12/09 06:00 [pubmed]
PHST- 2022/04/09 06:00 [medline]
PHST- 2021/12/07 00:00 [pmc-release]
AID - 10.1038/s41419-021-04419-8 [pii]
AID - 4419 [pii]
AID - 10.1038/s41419-021-04419-8 [doi]
PST - epublish
SO  - Cell Death Dis. 2021 Dec 7;12(12):1136. doi: 10.1038/s41419-021-04419-8.