Sahoo Soumya Swastik, Save Shreyada N, Madiwale Shantanu, Sharma Shilpy, Chugh Jeetender
Department of Chemistry, Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pashan, Pune 411008, India.
Department of Biotechnology, Savitribai Phule Pune University, Ganeshkhind Road, Pune 411007, India.
J Proteome Res. 2025 Aug 1;24(8):4202-4214. doi: 10.1021/acs.jproteome.5c00301. Epub 2025 Jul 10.
Type 1 diabetes mellitus (T1DM) is an autoimmune disorder caused by the loss of insulin-producing pancreatic β-cells. This study aims to explore the correlation between hyperglycemia and concurrent metabolic perturbations during T1DM development to help identify biomarkers that differentiate between the early and established stages. Streptozotocin (STZ), a glucosamine nitrosourea compound, induces T1DM. Dose- and time-dependent studies were conducted in 7-8-week-old male C57BL/6 mice, who were administered increasing numbers of STZ injections ( = 0-5) and were followed for 15 (early) and 60 (late) days. The development of hyperglycemia was confirmed by performing an oral glucose tolerance test and an insulin tolerance test. A total of 50 abundant aqueous serum metabolites were identified and quantified using H NMR spectroscopy. In addition to glucose, a well-established biomarker for T1DM, a panel of 5 significantly perturbed metabolites (namely, leucine, choline, lactate, lysine, and mannose), (DMF), was identified. Unlike glucose levels, the proposed DMF (in combination with glucose) could differentiate not only between early and established stages of T1DM but also between young and aged healthy controls. However, these results need validation in humanized animal models and well-characterized patient cohorts of different ethnicities. In conclusion, the results obtained have contributed toward increasing the understanding of the pathophysiology and mechanism of T1DM establishment and progression that would possibly aid in accurate diagnosis, prognosis, risk prediction, defining the distinct stages of T1DM, and help in enhancing patient outcomes in the future.
1型糖尿病（T1DM）是一种由产生胰岛素的胰腺β细胞缺失引起的自身免疫性疾病。本研究旨在探讨T1DM发展过程中高血糖与并发代谢紊乱之间的相关性，以帮助识别区分早期和已发病阶段的生物标志物。链脲佐菌素（STZ）是一种氨基葡萄糖亚硝基脲化合物，可诱发T1DM。对7 - 8周龄雄性C57BL/6小鼠进行剂量和时间依赖性研究，给它们注射数量逐渐增加的STZ（注射次数 = 0 - 5次），并跟踪观察15天（早期）和60天（晚期）。通过进行口服葡萄糖耐量试验和胰岛素耐量试验来确认高血糖的发展情况。使用核磁共振氢谱（H NMR）光谱法鉴定并定量了总共50种丰富的血清代谢物。除了作为T1DM公认生物标志物的葡萄糖外，还鉴定出一组5种显著受干扰的代谢物（即亮氨酸、胆碱、乳酸、赖氨酸和甘露糖），称为糖尿病代谢指纹（DMF）。与血糖水平不同，所提出的DMF（与葡萄糖结合）不仅可以区分T1DM的早期和已发病阶段，还可以区分年轻和老年健康对照。然而，这些结果需要在人源化动物模型和不同种族特征明确的患者队列中进行验证。总之，所获得的结果有助于加深对T1DM发生和发展的病理生理学及机制的理解，这可能有助于准确诊断、预后、风险预测、界定T1DM的不同阶段，并在未来改善患者的治疗效果。
