-
Tytuł:
-
The GLP-1 analog exendin-4 modulates HSP72 expression and ERK1/2 activity in BTC6 mouse pancreatic cells.
-
Autorzy:
-
Madhu D; Biochemistry and Molecular Biology Department, Dasman Diabetes Institute, Kuwait.
Khadir A; Genetics and Bioinformatics Department, Dasman Diabetes Institute, Kuwait.
Hammad M; Biochemistry and Molecular Biology Department, Dasman Diabetes Institute, Kuwait.
Kavalakatt S; Biochemistry and Molecular Biology Department, Dasman Diabetes Institute, Kuwait.
Dehbi M; Diabetes Research Centre, QBRI, Hamad Bin Khalifa University, Doha, Qatar.
Al-Mulla F; Genetics and Bioinformatics Department, Dasman Diabetes Institute, Kuwait.
Abubaker J; Biochemistry and Molecular Biology Department, Dasman Diabetes Institute, Kuwait.
Tiss A; Biochemistry and Molecular Biology Department, Dasman Diabetes Institute, Kuwait. Electronic address: .
-
Źródło:
-
Biochimica et biophysica acta. Proteins and proteomics [Biochim Biophys Acta Proteins Proteom] 2020 Jul; Vol. 1868 (7), pp. 140426. Date of Electronic Publication: 2020 Apr 07.
-
Typ publikacji:
-
Journal Article; Research Support, Non-U.S. Gov't
-
Język:
-
English
-
Imprint Name(s):
-
Original Publication: Amsterdam : Elsevier
-
MeSH Terms:
-
Exenatide/*metabolism
Glucagon-Like Peptide 1/*analogs & derivatives
HSP72 Heat-Shock Proteins/*metabolism
Insulin-Secreting Cells/*metabolism
MAP Kinase Signaling System/*physiology
Animals ; Apoptosis/drug effects ; Cell Line ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Diabetes Mellitus, Type 2/metabolism ; Endoplasmic Reticulum/drug effects ; Endoplasmic Reticulum/metabolism ; Exenatide/pharmacology ; HSP40 Heat-Shock Proteins ; Membrane Glycoproteins ; Mice ; Molecular Chaperones ; Phosphorylation ; Protective Agents/pharmacology ; Protein Interaction Maps ; Up-Regulation
-
Contributed Indexing:
-
Keywords: Diabetes; Glucagon-like peptide-1; Heat shock protein; Heat shock response; Mitogen-activated protein kinases; Proteomic profiling
-
Substance Nomenclature:
-
0 (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)
89750-14-1 (Glucagon-Like Peptide 1)
9P1872D4OL (Exenatide)
-
Entry Date(s):
-
Date Created: 20200410 Date Completed: 20200715 Latest Revision: 20200715
-
Update Code:
-
20240105
-
DOI:
-
10.1016/j.bbapap.2020.140426
-
PMID:
-
32272193
-
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.
Competing Interests: 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.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
