Sanford Burnham Prebys医学发现研究所和密歇根大学的研究人员发现，胰岛素分泌细胞依赖于一套精细的辅助蛋白系统来维持胰岛素的正常生成[1]。研究表明，当关键蛋白p58IPK缺失时，错误折叠的胰岛素前体蛋白会积累，最终导致细胞产生的胰岛素显著减少[1]。这项2026年6月1日发表于《美国国家科学院院刊》的研究揭示了蛋白质折叠缺陷与胰岛素生成障碍之间的深层联系[1]。
研究进一步明确了两种蛋白质在这一过程中的关键作用[1]。BiP和p58IPK必须协同工作才能维持正常的胰岛素生成，单独增加BiP无法弥补p58IPK的缺失[1]。在p58IPK缺失的小鼠模型中，β细胞产生的胰岛素前体和成熟胰岛素均明显下降[1]。现有糖尿病药物主要通过提高组织对葡萄糖的吸收或促进胰岛素分泌来控制疾病，并不直接纠正蛋白质折叠问题[1]。研究人员认为，加强细胞蛋白质折叠系统可能为保护胰腺β细胞并开发新型糖尿病疗法提供新的思路[1]。
Researchers have identified a critical protein support system that insulin-secreting cells rely upon to properly produce insulin.[1] When the key protein p58IPK is absent, misfolded insulin precursor proteins accumulate within cells, resulting in decreased insulin production.[1] The findings, published on June 1, 2026, in the Proceedings of the National Academy of Sciences, suggest that strengthening cellular protein-folding mechanisms could help protect pancreatic beta cells and offer new therapeutic avenues for diabetes treatment.[1]
The study, conducted by researchers from Sanford Burnham Prebys Medical Discovery Institute and the University of Michigan, reveals that two proteins—BiP and p58IPK—must work together to maintain proper insulin synthesis.[1] Critically, simply increasing BiP alone cannot compensate for the loss of p58IPK, indicating that both proteins play distinct and complementary roles.[1] In mouse models lacking p58IPK, beta cells produced reduced amounts of both insulin precursor and mature insulin.[1]
Current diabetes medications primarily address the disease by enhancing glucose uptake in tissues or promoting insulin secretion, rather than directly correcting the underlying protein-folding defects.[1] This research suggests that by targeting the cellular machinery responsible for proper insulin folding, a potentially new approach to diabetes management may be developed that goes beyond existing therapeutic strategies.