Increased hexosamine biosynthetic pathway flux alters cell-cell adhesion in INS-1E cells and murine islets.

Autor: Lofrumento DD; DiSTeBA, Centro Ecotekne, Strada Monteroni, University of Salento, 73100, Lecce, Italy., Miraglia A; DiSTeBA, Centro Ecotekne, Strada Monteroni, University of Salento, 73100, Lecce, Italy., La Pesa V; Institute of Experimental Neurology and Division of Neuroscience, Neuropathology Unit, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy., Treglia AS; DiSTeBA, Centro Ecotekne, Strada Monteroni, University of Salento, 73100, Lecce, Italy., Chieppa M; DiSTeBA, Centro Ecotekne, Strada Monteroni, University of Salento, 73100, Lecce, Italy., De Nuccio F; DiSTeBA, Centro Ecotekne, Strada Monteroni, University of Salento, 73100, Lecce, Italy., Nicolardi G; DiSTeBA, Centro Ecotekne, Strada Monteroni, University of Salento, 73100, Lecce, Italy., Miele C; CNR, IEOS and DiSMeT, Via S. Pansini 5, University 'Federico II', Naples, Italy., Beguinot F; CNR, IEOS and DiSMeT, Via S. Pansini 5, University 'Federico II', Naples, Italy., Garbi C; Dip. Medicina Molecolare e Biotecnologie Mediche, Via S. Pansini 5, University 'Federico II', Naples, Italy., Di Jeso B; DiSTeBA, Centro Ecotekne, Strada Monteroni, University of Salento, 73100, Lecce, Italy. bruno.dijeso@unisalento.it.
Jazyk: angličtina
Zdroj: Endocrine [Endocrine] 2023 Sep; Vol. 81 (3), pp. 492-502. Date of Electronic Publication: 2023 Jun 12.
DOI: 10.1007/s12020-023-03412-9
Abstrakt: Purpose: In type 2 Diabetes, β-cell failure is caused by loss of cell mass, mostly by apoptosis, but also by simple dysfunction (dedifferentiation, decline of glucose-stimulated insulin secretion). Apoptosis and dysfunction are caused, at least in part, by glucotoxicity, in which increased flux of glucose in the hexosamine biosynthetic pathway plays a role. In this study, we sought to clarify whether increased hexosamine biosynthetic pathway flux affects another important aspect of β-cell physiology, that is β-cell-β-cell homotypic interactions.
Methods: We used INS-1E cells and murine islets. The expression and cellular distribution of E-cadherin and β-catenin was evaluated by immunofluorescence, immunohistochemistry and western blot. Cell-cell adhesion was examined by the hanging-drop aggregation assay, islet architecture by isolation and microscopic observation.
Results: E-cadherin expression was not changed by increased hexosamine biosynthetic pathway flux, however, there was a decrease of cell surface, and an increase in intracellular E-cadherin. Moreover, intracellular E-cadherin delocalized, at least in part, from the Golgi complex to the endoplasmic reticulum. Beta-catenin was found to parallel the E-cadherin redistribution, showing a dislocation from the plasmamembrane to the cytosol. These changes had as a phenotypic consequence a decreased ability of INS-1E to aggregate. Finally, in ex vivo experiments, glucosamine was able to alter islet structure and to decrease surface abundandance of E-cadherin and β-catenin.
Conclusion: Increased hexosamine biosynthetic pathway flux alters E-cadherin cellular localization both in INS-1E cells and murine islets and affects cell-cell adhesion and islet morphology. These changes are likely caused by alterations of E-cadherin function, highlighting a new potential target to counteract the consequences of glucotoxicity on β-cells.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz: