The GLP-1 analog exendin-4 modulates HSP72 expression and ERK1/2 activity in BTC6 mouse pancreatic cells.
Animals
Apoptosis
/ drug effects
Cell Line
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Diabetes Mellitus, Type 2
/ metabolism
Endoplasmic Reticulum
/ drug effects
Exenatide
/ metabolism
Glucagon-Like Peptide 1
/ analogs & derivatives
HSP40 Heat-Shock Proteins
HSP72 Heat-Shock Proteins
/ metabolism
Insulin-Secreting Cells
/ metabolism
MAP Kinase Signaling System
/ physiology
Membrane Glycoproteins
Mice
Molecular Chaperones
Phosphorylation
Protective Agents
/ pharmacology
Protein Interaction Maps
Up-Regulation
Diabetes
Glucagon-like peptide-1
Heat shock protein
Heat shock response
Mitogen-activated protein kinases
Proteomic profiling
Journal
Biochimica et biophysica acta. Proteins and proteomics
ISSN: 1878-1454
Titre abrégé: Biochim Biophys Acta Proteins Proteom
Pays: Netherlands
ID NLM: 101731734
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
16
12
2019
revised:
09
03
2020
accepted:
02
04
2020
pubmed:
10
4
2020
medline:
16
7
2020
entrez:
10
4
2020
Statut:
ppublish
Résumé
Lipotoxicity, an important factor in the pathogenesis of diabetes, leads to defective β-cell proliferation and increased apoptosis. Glucagon-like peptide-1 (GLP-1) analogs, which are used to treat type 2 diabetes, reduce endoplasmic reticulum stress and inflammation in pancreatic β-cells and improve their survival. However, their effects on the heat shock response (HSR) have not been elucidated yet. We investigated whether the GLP-1 analog exendin-4 exerts its protective effect by modulating the HSR and mitogen-activated protein kinases (MAPKs) in BTC-6 mouse pancreatic cells under palmitic acid (PA) stress. Expression patterns were analyzed using mass spectrometry, Western blotting, and qRT-PCR in the presence of 250 or 400 μM PA and 100 nM exendin-4. Additionally, we measured MAPK expression and phosphorylation using qRT-PCR and Western blotting, respectively. Upregulation of heat shock protein (HSP), notably HSP72, in the presence of PA, was attenuated by exendin-4. Despite the absence of global effects on the HSR system, exendin-4 attenuated the expression of other non-classical HSPs (GRP94, DNAJA1, and DNAJB6) in the presence of PA. Regarding MAPKs, only extracellular signal-regulated kinase (ERK) phosphorylation was highly increased by exendin-4 in both the presence and absence of PA. Furthermore, exendin-4 significantly alleviated PA-induced cell death, which was further confirmed with proteomics analysis where key cellular functions, including cellular growth, assembly, and organization, were improved by exendin-4 treatment. Thus, our results expand the protective role of GLP-1 analogs to include other cellular mechanisms involved in restoring normal β-cell homeostasis.
Identifiants
pubmed: 32272193
pii: S1570-9639(20)30073-X
doi: 10.1016/j.bbapap.2020.140426
pii:
doi:
Substances chimiques
Dnaja1 protein, mouse
0
Dnajb6 protein, mouse
0
HSP40 Heat-Shock Proteins
0
HSP72 Heat-Shock Proteins
0
Membrane Glycoproteins
0
Molecular Chaperones
0
Protective Agents
0
endoplasmin
0
Glucagon-Like Peptide 1
89750-14-1
Exenatide
9P1872D4OL
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
140426Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.