Diabetes, characterized by elevated blood sugar levels, often leads to various complications. Cysteine (Cys), a biomarker of oxidative stress, is crucial in the progression of diabetes and its complications. Unfortunately, up until now, fluorescent probes for imaging lysosomal Cys in diabetic mouse models have not been available. Ferroptosis, linked to antioxidant damage in the lysosomal Cys/GPX4 axis, plays a significant role in diabetes. Visualizing lysosomal Cys is vital for assessing ferroptosis and understanding diabetes. We introduce a new near-infrared (NIR) fluorescent probe, , designed to detect lysosomal Cys in living cells and diabetic mouse models. This probe shows exceptional selectivity and sensitivity towards Cys, along with superior fluorescence characteristics, enabling detection of Cys in living cells. can monitor ferroptosis and its inhibition by measuring lysosomal Cys levels and has been used to detect ferroptosis in glucose-induced diabetic cells. It revealed significantly lower Cys concentrations in the livers of diabetic mice compared to healthy controls. Administering antidiabetic medication increased Cys production in diabetic mice. These findings highlight the potential of as a tool for elucidating the role of Cys in lysosome-related diseases, providing critical insights into diagnosis and treatment strategies for diabetes and its complications.

中文翻译：

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用溶酶体靶向近红外荧光探针监测糖尿病小鼠的半胱氨酸变化并评估铁死亡


糖尿病的特点是血糖水平升高，通常会导致各种并发症。半胱氨酸 (Cys) 是氧化应激的生物标志物，在糖尿病及其并发症的进展中至关重要。不幸的是，到目前为止，还没有用于糖尿病小鼠模型中溶酶体半胱氨酸成像的荧光探针。铁死亡与溶酶体 Cys/GPX4 轴的抗氧化损伤有关，在糖尿病中起着重要作用。溶酶体半胱氨酸的可视化对于评估铁死亡和了解糖尿病至关重要。我们推出了一种新的近红外 (NIR) 荧光探针，旨在检测活细胞和糖尿病小鼠模型中的溶酶体 Cys。该探针对 Cys 表现出卓越的选择性和灵敏度，以及卓越的荧光特性，能够检测活细胞中的 Cys。可以通过测量溶酶体半胱氨酸水平来监测铁死亡及其抑制，并已用于检测葡萄糖诱导的糖尿病细胞中的铁死亡。结果显示，与健康对照组相比，糖尿病小鼠肝脏中的半胱氨酸浓度显着降低。服用抗糖尿病药物会增加糖尿病小鼠体内半胱氨酸的产生。这些发现凸显了作为阐明 Cys 在溶酶体相关疾病中的作用的工具的潜力，为糖尿病及其并发症的诊断和治疗策略提供了重要的见解。