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Test-Time Deep Thinking to Explore Implicit Rules
Contextual Rollout Bandits for Reinforcement Learning with Verifiable Rewards
ATP2B4 driven chromatin compaction exacerbates pancreatic cancer radiotherapy resistance
Cell Death Discovery, Published online: 25 May 2026; doi:10.1038/s41420-026-03142-7
ATP2B4 driven chromatin compaction exacerbates pancreatic cancer radiotherapy resistanceMetformin suppresses β-cell apoptosis under ER stress by inhibiting protein translation
Metabolism. 2026 Apr 8:156607. doi: 10.1016/j.metabol.2026.156607. Online ahead of print.
ABSTRACT
Endoplasmic reticulum (ER) stress is a critical driver of pancreatic β-cell dysfunction and apoptosis. Although metformin, a drug used to treat type 2 diabetes, primarily decreases blood glucose levels by improving insulin sensitivity, its direct effects on β-cell survival remain unclear. Here, we investigated the effect of metformin on β-cell stress responses under ER stress conditions. Thapsigargin (Tg)-induced ER stress increased β-cell apoptosis in mouse islets, which was prevented by metformin in a dose-dependent manner. Treatment with metformin for 24 h suppressed the Tg-induced upregulation of unfolded protein response (UPR)-related genes, as confirmed by transcriptomic and pathway analyses. Quantitative proteomics revealed that Tg inhibited eIF2 signaling and protein translation, both of which were partially restored by metformin. Enrichment analysis further indicated the attenuation of apoptotic pathways in metformin-treated islets. Polysome profiling and puromycin incorporation assays demonstrated that metformin reduced protein translation independently of ER stress. Metformin promoted the dephosphorylation of 4E-BP1, a key initiator of cap-dependent protein translation that is activated by phosphorylation, and the antiapoptotic effect of metformin was abolished by 4E-BP1 knockdown in MIN6 cells. Phosphoproteomic analysis indicated that the activation of mTOR signaling, a kinase of 4E-BP1, in Tg-treated islets was mitigated by metformin. Taken together, these findings reveal a cytoprotective mechanism of metformin in β-cells, in which metformin suppresses ER stress-induced apoptosis through 4E-BP1-mediated inhibition of mRNA translation and modulation of mTOR signaling. This study highlights a β-cell-intrinsic action of metformin that may contribute to its long-term therapeutic benefits in diabetes management.
PMID:41962652 | DOI:10.1016/j.metabol.2026.156607
ATBench: A Diverse and Realistic Trajectory Benchmark for Long-Horizon Agent Safety
A Comprehensive Graph Pooling Benchmark: Effectiveness, Robustness and Generalizability
Long-Document QA with Chain-of-Structured-Thought and Fine-Tuned SLMs
Nanoscale transfer-printed full-colour ultrahigh-resolution quantum dot LEDs
Nature, Published online: 01 April 2026; doi:10.1038/s41586-026-10333-w
A dual-action force dynamics strategy using a hard silicon template as a nanoimprinting stamp combined with inverted transfer printing is described for the manufacture of high-performance full-colour ultrahigh-resolution quantum dot light-emitting diodes (LEDs) for active-matrix displays, while revealing electric-field reconstruction in nanoscale arrays and introducing dielectric matching to mitigate field concentration and performance degradation.