Glucotoxicity is mediated by cytoplasmic distribution of RAP1 in pancreatic β-cells

A Deręgowska; N Tomaszek; P Cuch; K Kozioł; O Kaniuka; M Sabadashka; Yu Bandura; N Sybirna

doi:10.1016/j.abb.2024.109982

Glucotoxicity is mediated by cytoplasmic distribution of RAP1 in pancreatic β-cells

Arch Biochem Biophys. 2024 May:755:109982. doi: 10.1016/j.abb.2024.109982. Epub 2024 Apr 1.

Authors

A Deręgowska¹, N Tomaszek², P Cuch², K Kozioł², O Kaniuka³, M Sabadashka³, Yu Bandura³, N Sybirna³

Affiliations

¹ Institute of Biotechnology, College of Natural Sciences, University of Rzeszow, Pigonia 1, 35-310, Rzeszow, Poland. Electronic address: aderegowska@ur.edu.pl.
² Institute of Biotechnology, College of Natural Sciences, University of Rzeszow, Pigonia 1, 35-310, Rzeszow, Poland.
³ Department of Biochemistry, Ivan Franko National University of Lviv, 1, Universytetska St., 79000, Lviv, Ukraine.

PMID: 38570110
DOI: 10.1016/j.abb.2024.109982

Abstract

Diabetes mellitus (DM) is a group of chronic metabolic disorders characterized by persistent hyperglycemia. In our study, we analyzed the level and location of RAP1 changes in the development of β-cell dysfunction induced by glucotoxicity. We employed three pancreatic β-cell lines, namely INS-1, 1.2B4, and NIT-1, as well as a streptozotocin-induced diabetes rat model. We demonstrate that after high glucose treatment, RAP1 is increased, probably through induction by AKT, allowing RAP1 to shuttle from the nucleus to the cytoplasm and activate NF-κB signaling. Furthermore, non-enzymatic post-translational modifications of RAP1, such as advanced glycation end products and carbonylation may affect the function of RAP1, such as activation of the NF-κB signaling. Taken together, we showed that RAP1 is a new player in the mechanism of glucotoxicity in pancreatic β-cells.

Keywords: Diabetes mellitus; High glucose treatment; Pancreatic β-cells; RAP1.