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The impact of the glucagon-like peptide 1 receptor agonist liraglutide on the streptozotocin-induced diabetic mouse kidney proteome

Liljedahl, Leena LU ; Pedersen, Maiken H.; McGuire, James N. and James, Peter LU (2019) In Physiological Reports 7(4).
Abstract

In diabetes mellitus (DM), the kidneys are exposed to increased levels of hyperglycemia-induced oxidative stress. Elevated amounts of reactive oxygen species (ROS) are believed to provoke ultrastructural changes in kidney tissue and can eventually result in DM late complications such as diabetic nephropathy. While it is reported that glucagon-like peptide 1 receptors (GLP-1R) are present in the kidney vasculature, the effects of GLP-1 on the kidney proteome in DM is not well described. Thus, we set out to investigate potential effects on the proteomic level. Here the effects of GLP-1R agonism using the GLP-1 analogue liraglutide are studied in the kidneys of streptozotocin (STZ)-treated mice (n = 6/group) by label-free shotgun mass... (More)

In diabetes mellitus (DM), the kidneys are exposed to increased levels of hyperglycemia-induced oxidative stress. Elevated amounts of reactive oxygen species (ROS) are believed to provoke ultrastructural changes in kidney tissue and can eventually result in DM late complications such as diabetic nephropathy. While it is reported that glucagon-like peptide 1 receptors (GLP-1R) are present in the kidney vasculature, the effects of GLP-1 on the kidney proteome in DM is not well described. Thus, we set out to investigate potential effects on the proteomic level. Here the effects of GLP-1R agonism using the GLP-1 analogue liraglutide are studied in the kidneys of streptozotocin (STZ)-treated mice (n = 6/group) by label-free shotgun mass spectrometry (MS) and targeted MS. Unsupervised and supervised multivariate analyses are followed by one-way ANOVA. Shotgun MS data of vehicle and liraglutide-treated mouse groups are separated in the supervised multivariate analysis and separation is also achieved in the subsequent unsupervised multivariate analysis using targeted MS data. The mouse group receiving the GLP-1R agonist liraglutide has increased protein abundances of glutathione peroxidase-3 (GPX3) and catalase (CATA) while the abundances of neuroplastin (NPTN) and bifunctional glutamate/proline–tRNA ligase (SYEP) are decreased compared to the STZ vehicle mice. The data suggest that GLP-1R agonism mainly influences abundances of structurally involved proteins and proteins involved in oxidative stress responses in the STZ mouse kidney. The changes could be direct effects of GLP-1R agonism in the kidneys or indirectly caused by a systemic response to GLP-1R activation.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Diabetic kidney damage, GLP-1R agonist, kidney proteome, liraglutide
in
Physiological Reports
volume
7
issue
4
publisher
John Wiley & Sons
external identifiers
  • scopus:85062183649
ISSN
2051-817X
DOI
10.14814/phy2.13994
language
English
LU publication?
yes
id
e3d24001-0e20-42a3-8180-5c2de38ed361
date added to LUP
2019-03-11 12:40:24
date last changed
2019-04-02 04:14:47
@article{e3d24001-0e20-42a3-8180-5c2de38ed361,
  abstract     = {<p>In diabetes mellitus (DM), the kidneys are exposed to increased levels of hyperglycemia-induced oxidative stress. Elevated amounts of reactive oxygen species (ROS) are believed to provoke ultrastructural changes in kidney tissue and can eventually result in DM late complications such as diabetic nephropathy. While it is reported that glucagon-like peptide 1 receptors (GLP-1R) are present in the kidney vasculature, the effects of GLP-1 on the kidney proteome in DM is not well described. Thus, we set out to investigate potential effects on the proteomic level. Here the effects of GLP-1R agonism using the GLP-1 analogue liraglutide are studied in the kidneys of streptozotocin (STZ)-treated mice (n = 6/group) by label-free shotgun mass spectrometry (MS) and targeted MS. Unsupervised and supervised multivariate analyses are followed by one-way ANOVA. Shotgun MS data of vehicle and liraglutide-treated mouse groups are separated in the supervised multivariate analysis and separation is also achieved in the subsequent unsupervised multivariate analysis using targeted MS data. The mouse group receiving the GLP-1R agonist liraglutide has increased protein abundances of glutathione peroxidase-3 (GPX3) and catalase (CATA) while the abundances of neuroplastin (NPTN) and bifunctional glutamate/proline–tRNA ligase (SYEP) are decreased compared to the STZ vehicle mice. The data suggest that GLP-1R agonism mainly influences abundances of structurally involved proteins and proteins involved in oxidative stress responses in the STZ mouse kidney. The changes could be direct effects of GLP-1R agonism in the kidneys or indirectly caused by a systemic response to GLP-1R activation.</p>},
  articleno    = {e13994},
  author       = {Liljedahl, Leena and Pedersen, Maiken H. and McGuire, James N. and James, Peter},
  issn         = {2051-817X},
  keyword      = {Diabetic kidney damage,GLP-1R agonist,kidney proteome,liraglutide},
  language     = {eng},
  number       = {4},
  publisher    = {John Wiley & Sons},
  series       = {Physiological Reports},
  title        = {The impact of the glucagon-like peptide 1 receptor agonist liraglutide on the streptozotocin-induced diabetic mouse kidney proteome},
  url          = {http://dx.doi.org/10.14814/phy2.13994},
  volume       = {7},
  year         = {2019},
}