The synthesis, processing, and secretion of insulin by the pancreatic β-cell is key for the maintenance of systemic metabolic homeostasis, and loss or dysfunction of β-cells underlies the development of both type 1 diabetes (T1D) and type 2 diabetes (T2D). Work in the Evans-Molina laboratory over the past 15 years has pioneered the idea that regulation of calcium dynamics is critical to β-cell biology and diabetes pathophysiology. In this article, I will share three vignettes from the laboratory that demonstrate our bench-to-bedside approach to determining mechanisms of β-cell stress that could improve therapeutic options and outcomes for individuals living with diabetes. The first of these vignettes will illustrate a role for the sarcoendoplasmic reticulum calcium ATPase (SERCA) pump in the regulation of endoplasmic reticulum (ER) calcium, protein trafficking, and proinsulin processing within the β-cell. The second vignette will highlight how alterations in β-cell calcium signaling intersect with T1D pathogenesis. The final vignette will demonstrate how activation of β-cell stress pathways may serve as an anchor to inform biomarker strategies in T1D. Lastly, I will share my vision for the future of diabetes care, where multiple biomarkers of β-cell stress may be combined with additional immune and metabolic biomarkers to better predict disease risk and improve therapies to prevent or delay T1D development.

中文翻译：

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糖尿病中患病的 β 细胞：急诊室之旅的见解：2023 年杰出科学成就奖讲座

胰腺 β 细胞合成、加工和分泌胰岛素是维持全身代谢稳态的关键，β 细胞的损失或功能障碍是 1 型糖尿病 (T1D) 和 2 型糖尿病 (T2D) 发展的基础。 ）。 Evans-Molina 实验室过去 15 年的工作开创了这样的观点：钙动力学的调节对于 β 细胞生物学和糖尿病病理生理学至关重要。在本文中，我将分享实验室的三个小故事，展示我们从实验室到临床的方法来确定 β 细胞应激机制，从而改善糖尿病患者的治疗选择和结果。第一个小插图将说明肌内质网钙 ATP 酶 (SERCA) 泵在调节内质网 (ER) 钙、蛋白质运输和 β 细胞内胰岛素原加工中的作用。第二个小插曲将强调 β 细胞钙信号传导的改变如何与 T1D 发病机制相交叉。最后的小插图将展示 β 细胞应激通路的激活如何作为锚定来为 T1D 的生物标志物策略提供信息。最后，我将分享我对糖尿病护理未来的愿景，其中 β 细胞应激的多种生物标志物可以与其他免疫和代谢生物标志物相结合，以更好地预测疾病风险并改进治疗方法以预防或延缓 T1D 的发展。