Excess Fructose Intake Activates Hyperinsulinemia and Mitogenic MAPK Pathways in Association With Cellular Stress, Inflammation, and Apoptosis in the Pancreas of Rats

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dc.authoridGUNEY, Ceren/0000-0002-3267-2886
dc.authoridAkar, Fatma/0000-0002-5432-0304
dc.contributor.authorGuney, Ceren
dc.contributor.authorAlcigir, Mehmet Eray
dc.contributor.authorAkar, Fatma
dc.date.accessioned2025-10-11T20:48:48Z
dc.date.available2025-10-11T20:48:48Z
dc.date.issued2025
dc.departmentDüzce Üniversitesien_US
dc.description.abstractThe increase in sugar consumption has been associated with current metabolic disease epidemics. This study aimed to investigate the pancreatic molecular mechanisms involved in cellular stress, inflammation, mitogenesis, and apoptosis in metabolic disease induced by high-fructose diet. Here, we used biochemical, histopathological, Western blot, and immunohistochemistry methods to determine the metabolic and pancreatic alterations in male Wistar rats fed 20% fructose in drinking water for 15 weeks. High-fructose consumption in rats increased the immunopositivity and protein expression of glucose transporter 2 (GLUT2) and insulin in the pancreatic tissue, in association with abdominal adiposity, hyperglycemia, and hypertriglyceridemia. The expressions of cellular stress markers, glucose-regulated protein-78 (GRP78) and PTEN-induced putative kinase 1 (PINK1), were increased in the pancreas. The levels of interleukin (IL)-6, nuclear factor kappa B (NF kappa B), tumor necrosis factor alpha (TNF alpha), and IL-1 beta and components of the Nod-like receptor protein 3 (NLRP3) inflammasome were elevated. Excess fructose intake stimulated the activation of mitogenic extracellular signal-regulated kinases 1/2 (ERK1/2), p38, and c-Jun N-terminal kinase (JNK)1 as well as the apoptotic p53 and Fas pathways in the pancreas of rats. There was also an increase in caspase-8 and caspase-3 cleavage. Our findings revealed that dietary high-fructose in the pancreas causes hyperinsulinemia due to the upregulation of GLUT2 together with cellular stress and inflammatory markers, thereby stimulates mitogenic mitogen-activated protein kinase (MAPK) and apoptosis pathways, resulting in a complex pathological situation.en_US
dc.description.sponsorshipGazi University Research Funden_US
dc.description.sponsorshipTurkish Council of Higher Education (YOK)en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkiye (TUBITAK)en_US
dc.description.sponsorshipThis study was supported by grants from the Gazi University Research Fund (TDK-2022-7661). Ceren Guney thanks the Turkish Council of Higher Education (YOK) and Scientific and Technological Research Council of Turkiye (TUBITAK) for PhD scholarships (100/2000 and BIDEB 2211-A).en_US
dc.identifier.doi10.1002/mnfr.70048
dc.identifier.issn1613-4125
dc.identifier.issn1613-4133
dc.identifier.issue10en_US
dc.identifier.pmid40152093en_US
dc.identifier.scopus2-s2.0-105001715164en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1002/mnfr.70048
dc.identifier.urihttps://hdl.handle.net/20.500.12684/22115
dc.identifier.volume69en_US
dc.identifier.wosWOS:001455668900001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofMolecular Nutrition & Food Researchen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmzKA_WOS_20250911
dc.subjectapoptosisen_US
dc.subjectcellular stressen_US
dc.subjectdietary fructoseen_US
dc.subjectinflammationen_US
dc.subjectpancreatic mitogenesisen_US
dc.titleExcess Fructose Intake Activates Hyperinsulinemia and Mitogenic MAPK Pathways in Association With Cellular Stress, Inflammation, and Apoptosis in the Pancreas of Ratsen_US
dc.typeArticleen_US

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