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Insulin oxidation and oxidative modifications alter glucose uptake, cell metabolism, and inflammatory secretion profiles

Authors :
Ramona Clemen
Wiebke Dethloff
Julia Berner
Paul Schulan
Alice Martinet
Klaus Dieter Weltmann
Thomas von Woedtke
Tilman Grune
Kristian Wende
Sander Bekeschus
Source :
Redox Biology, Vol 77, Iss , Pp 103372- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Insulin participates in glucose homeostasis in the body and regulates glucose, protein, and lipid metabolism. Chronic hyperglycemia triggers oxidative stress and the generation of reactive oxygen species (ROS), leading to oxidized insulin variants. Oxidative protein modifications can cause functional changes or altered immunogenicity as known from the context of autoimmune disorders. However, studies on the biological function of native and oxidized insulin on glucose homeostasis and cellular function are lacking. Native insulin showed heterogenous effects on metabolic activity, proliferation, glucose carrier transporter (GLUT) 4, and insulin receptor (INSR) expression, as well as glucose uptake in cell lines of five different human tissues. Diverse ROS compositions produced by different gas plasma approaches enabled the investigations of variously modified insulin (oxIns) with individual oxidative post-translational modification (oxPTM) patterns as identified using high-resolution mass spectrometric analysis. Specific oxIns variants promoted cellular metabolism and proliferation in several cell lines investigated, and nitrogen plasma emission lines could be linked to insulin nitration and elevated glucose uptake. In addition, insulin oxidation modified blood glucose levels in the chicken embryos (in ovo), underlining the importance of assessing protein oxidation and function in health and disease.

Details

Language :
English
ISSN :
22132317
Volume :
77
Issue :
103372-
Database :
Directory of Open Access Journals
Journal :
Redox Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.f910362de216412a848816c5c1bf2735
Document Type :
article
Full Text :
https://doi.org/10.1016/j.redox.2024.103372