What question did this study set out to answer?

This research aims to understand how pancreatic β cells rapidly adjust protein synthesis in response to glucose.

June 7, 2026

2685-P: Acute Glucose Stimulation Drives Coordinated Translational Reprogramming in Primary Pancreatic Islets: From Global Remodeling to Fine-Tuned Insulin Synthesis

Key Points

This research aims to understand how pancreatic β cells rapidly adjust protein synthesis in response to glucose.
Mouse islets were incubated in two glucose concentrations (2.5 mM and 25 mM) for 2 hours.
Ribosome profiling was conducted, with 100ug/mL cycloheximide administered before sample collection for 15 minutes.
Differential gene expression was analyzed using a fold change threshold of >1.5 and a p-value <0.05.
1,680 differentially expressed genes were identified, indicating extensive translational reprogramming (p<0.05).
High glucose conditions led to the upregulation of immediate-early genes and downregulation of stress-related factors.
The study found increased mRNA stability and a relief of SRP-mediated elongation arrest on Ins1/2 mRNAs under high glucose.

Abstract

Introduction and Objective: Pancreatic β cells must rapidly augment protein synthesis to maintain systemic glycemic homeostasis; yet, the immediate translational dynamics governing this adaptive phase remain poorly defined. Methods: In this study, mouse islets were incubated in either 2.5 mM or 25 mM glucose for 2 hours and subjected to ribosome profiling. 100ug/mL cycloheximide was added before sample collection for 15 minutes. Results: We identified 1,680 differentially expressed genes (fold change threshold 1.5 and p-value 0.05), indicating an extensive translational reprogramming. The most striking changes include the upregulation of immediated-early-genes (e.g., Nr4a1, Fos) and the downregulation of stress-related factors (e.g., Trib3, Ddit3, Atf4). Furthermore, high glucose expanded the cytosolic translation machinery, accelerated translation kinetics, increased mRNA stability and quality control system. Intriguingly, beyond simply promoting the ribosome recruitment, ribosomal footprint analysis revealed a prominent relief of Signal Recognition Particle (SRP)-mediated elongation arrest on Ins1/2 mRNAs in high glucose. Finally, β cells adopted an “efficiency-over-expansion” model, maximizing the oxidative capacity of existing mitochondria to fulfill immediate energy demands while suppressing de novo mitochondrial biogenesis. This ensures the prioritization of resources and prevents excessive oxidative stress. Conclusion: In summary, our research characterizes the translatome as a dynamic and qualitative regulator of nutritional adaptation and identifies specific molecular nodes essential for preserving β cell function in Type 2 Diabetes. Disclosure Y. Wang: None. Y. Liu: None. C. Shi: None. M. Liu: None. X. Xu: None. Funding National Key R&D Program (2024YFA1802903), National Natural Science Foundation of China (82370821)(82220108014), Tianjin Medical University General Hospital Clinical Research Program (22ZYYLCZD02), Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-3-002C), Tianjin Medical University Clinical Special Disease Research Center - Neuroendocrine Tumor Clinical Special Disease Research Center.

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