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Peter James

Peter James

Professor

Peter James

N-glycosylation proteome enrichment analysis in kidney reveals differences between diabetic mouse models

Author

  • Leena Liljedahl
  • Maiken Højgaard Pedersen
  • Jenny Norlin
  • James N. McGuire
  • Peter James

Summary, in English

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.

Department/s

  • Department of Immunotechnology

Publishing year

2016-10-15

Language

English

Publication/Series

Clinical Proteomics

Volume

13

Issue

1

Document type

Journal article

Publisher

Humana Press

Topic

  • Medicinal Chemistry
  • Endocrinology and Diabetes

Keywords

  • db/db
  • Diabetic nephropathy
  • Glomerulus
  • Insulin
  • Mass spectrometry
  • N-glycosylation
  • N-linked glycosylation
  • Proximal tubules
  • STZ

Status

Published

ISBN/ISSN/Other

  • ISSN: 1542-6416