Objective: To investigate the cellular memory of previous high glucose exposure in rat islet cell line (INS-1) and explore the possible mechanism.
Methods: INS-1 cells were exposed to a high glucose (33.3 mmol/L) culture for 48 h followed by further culture in the presence of 11.1 mmol/L glucose in the culture medium for 3 or 5 days. The levels of bax and caspase-3 mRNA were measured by real-time PCR, the production of reactive oxygen species (ROS) was assayed using the dihydroethidium probe, and the cell viability was detected by MTT assay.
Results: High glucose exposure of the cells for 48 h resulted in significantly increased ROS production and bax and caspase-3 mRNA expressions and lowered cell viability (P<0.001). In cells cultured in 11.1 mmol/L glucose following previous high glucose exposure, the ROS production and bax and caspase-3 mRNA expressions still maintained the high levels (P<0.05) while the cell viability remained significantly lower than the control cells (P<0.001).
Conclusion: High glucose causes persistent changes in cell viability and apoptosis-related gene expressions even after recovery of normoglycemia, the mechanism of which is probably related to increased ROS production.
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Sci Adv
January 2025
Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
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Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China; Research Center for Industries of the Future, Westlake University, Hangzhou, Zhejiang, China. Electronic address:
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Department of Material Sciences, Institute of Pure and Applied Sciences, University of Tsukuba, 1-1-1, Tennodai, Ibaraki 305-5358, Japan.
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Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Diabetes is a major risk factor for cardiovascular disease, but the molecular mechanisms underlying diabetic vasculopathy have been elusive. Here we report that inositol hexakisphosphate kinase 1 (IP6K1) mediates hyperglycemia-induced endothelial senescence by rewiring the liver kinase B1 (LKB1) signaling from activating the adenosine monophosphate-activated protein kinase (AMPK) pathway to the p53 pathway. We found that hyperglycemia upregulated IP6K1, which disrupts the Hsp/Hsc70 and carboxyl terminus of Hsc70-interacting protein (CHIP)-mediated LKB1 degradation, leading to increased expression levels of LKB1.
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Groupe de Recherche en Signalisation Cellulaire (GRSC), Département de Biologie Médicale, Université du Québec à Trois-Rivières, 3351 Boulevard des Forges, Trois-Rivières, QC G8Z 4M3, Canada.
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