| 1. |
- Liljedahl, Leena, et al.
(författare)
-
Effects of insulin and the glucagon-like peptide 1 receptor agonist liraglutide on the kidney proteome in db/db mice.
- 2017
-
Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 5:6
-
Tidskriftsartikel (refereegranskat)abstract
- Diabetes mellitus (DM) is a worldwide disease that affects 9% of the adult world population and type 2 DM accounts for 90% of those. A common consequence of DM is kidney complications, which could lead to kidney failure. We studied the potential effects of treatment with insulin and the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide on the diabetic kidney proteome through the use of the db/db mouse model system and mass spectrometry (MS). Multivariate analyses revealed distinct effects of insulin and liraglutide on the db/db kidney proteome, which was seen on the protein levels of, for example, pterin-4 α-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor-1α (PCBD1), neural precursor cell expressed developmentally down-regulated-8 (NEDD8), transcription elongation factor-B polypeptide-1 (ELOC) and hepcidin (HEPC). Furthermore, the separation of the insulin, liraglutide and vehicle db/db mouse groups in multivariate analyses was not mainly related to the albumin excretion rate (AER) or the level of glycated hemoglobin A1c (HbA1c%) in the mice. In summary, we show that insulin and liraglutide give rise to separate protein profiles in the db/db mouse kidney.
|
|
| 2. |
- Liljedahl, Leena
(författare)
-
Exploring the diabetic kidney proteome : A junction of tissue and serum
- 2016. - 1
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diabetic kidney disease is one of the major complications associated with diabetes. Approximately 25-40% of both type 1 and type 2 diabetes patients will acquire a kidney complication and despite global efforts to reduce the prevalence of diabetic kidney disease, it is a leading cause of kidney failure in the western world. There are few treatment options directly targeting the kidney.The overall aim of this thesis was to dig past the current state of knowledge and delve deeper into the proteomic profile of diabetic kidney disease. By the use of discovery based and targeted mass spectrometry, the kidney proteomes of two diabetic mouse models reflecting type 1 and type 2 diabetes with early kidney disease were investigated and the serum proteomes of diabetes patients with various degrees of albuminuria were compared. In summary, the majority of the changes were seen for proteins with expression in the tubules, the reabsorbing organ in the kidneys and not in the glomeruli, which is the filtering unit. The findings in this thesis could imply that we need to re-think the target of kidney medication and the importance of tubuloglomerular feedback.
|
|
| 3. |
- Liljedahl, Leena, et al.
(författare)
-
N-glycosylation proteome enrichment analysis in kidney reveals differences between diabetic mouse models
- 2016
-
Ingår i: Clinical Proteomics. - : Springer Science and Business Media LLC. - 1542-6416 .- 1559-0275. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. Already at an early stage of DN morphological changes occur at the cell surface and in the extracellular matrix where the majority of the proteins carry N-linked glycosylations. These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. Method: We enriched for the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle, in streptozotocin-induced (STZ) diabetic mice and healthy control mice dosed with vehicle. Glycopeptides were analyzed with label-free shotgun mass spectrometry and differential protein abundances identified in both mouse models were compared using multivariate analyses. Results: The majority of the N-glycosylated proteins were similarly regulated in both mouse models. However, distinct differences between the two mouse models were for example seen for integrin-β1, a protein expressed mainly in the glomeruli which abundance was increased in the STZ diabetic mice while decreased in the db/db mice and for the sodium/glucose cotransporter-1, mainly expressed in the proximal tubules which abundance was increased in the db/db mice but decreased in the STZ diabetic mice. Insulin had an effect on the level of both glomerular and tubular proteins in the db/db mice. It decreased the abundance of G-protein coupled receptor-116 and of tyrosine-protein phosphatase non-receptor type substrate-1 away from the level in the healthy control mice. Conclusions: Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. Thus, N-glycosylated protein differences could be a clue to dissimilarities in T1DM and T2DM at later stages of DN. Furthermore, we observed insulin specific regulation of N-glycosylated proteins both in the direction of and away from the abundances in healthy control mice.
|
|
| 4. |
- Liljedahl, Leena, et al.
(författare)
-
The impact of the glucagon-like peptide 1 receptor agonist liraglutide on the streptozotocin-induced diabetic mouse kidney proteome
- 2019
-
Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 7:4
-
Tidskriftsartikel (refereegranskat)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 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.
|
|
