Xu Wenxin, Wu Junfang, An Yanpeng, Xiao Chaoni, Hao Fuhua, Liu Hongbing, Wang Yulan, Tang Huiru
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences , Wuhan 430071, People's Republic of China.
J Proteome Res. 2012 Jun 1;11(6):3423-35. doi: 10.1021/pr300280t. Epub 2012 May 18.
Diabetes mellitus is a complex polygenic disease caused by gene-environment interactions with multiple complications, and metabonomic analysis is crucial for pathogenesis, early diagnosis, and timely interventions. Here, we comprehensively analyzed the dynamic metabolic changes in rat urine and plasma, which were induced by the well-known diabetogenic chemical streptozotocin (STZ), using (1)H NMR spectroscopy in conjunction with multivariate data analysis. The results showed that a single intraperitoneal injection of STZ with a moderate dosage (55 mg/kg) induced significant urinary metabonomic changes within 24 h. These changes showed time-dependence and heterogeneity among the treated animals with an animal recovered within 11 days. STZ-induced metabonomic alterations were related to suppression of glycolysis and TCA cycle, promotion of gluconeogenesis and oxidation of amino acids, alterations in metabolisms of basic amino acids associated with diabetic complications, and disruption of lipid metabolism and gut microbiota functions. With diffusion-edited NMR spectral data, we further observed the STZ-induced significant elevation of monounsaturated fatty acids and total unsaturated fatty acids together with reductions in PUFA-to-MUFA ratio in the blood plasma. These findings provided details of the time-dependent metabonomic changes in the progressive development of the STZ-induced diabetes mellitus and showed the possibility of detecting the biochemical changes in the early stage of type 1 diabetic genesis.
糖尿病是一种由基因与环境相互作用引起的复杂多基因疾病，伴有多种并发症，代谢组学分析对于其发病机制、早期诊断和及时干预至关重要。在此，我们使用核磁共振氢谱结合多变量数据分析，全面分析了由著名的致糖尿病化学物质链脲佐菌素（STZ）诱导的大鼠尿液和血浆中的动态代谢变化。结果表明，单次腹腔注射中等剂量（55 mg/kg）的STZ在24小时内可诱导显著的尿液代谢组学变化。这些变化在治疗动物中呈现出时间依赖性和异质性，其中一只动物在11天内恢复。STZ诱导的代谢组学改变与糖酵解和三羧酸循环的抑制、糖异生和氨基酸氧化的促进、与糖尿病并发症相关的碱性氨基酸代谢改变以及脂质代谢和肠道微生物群功能的破坏有关。通过扩散编辑的核磁共振光谱数据，我们进一步观察到STZ诱导血浆中单不饱和脂肪酸和总不饱和脂肪酸显著升高，同时多不饱和脂肪酸与单不饱和脂肪酸的比率降低。这些发现提供了STZ诱导的糖尿病进行性发展过程中随时间变化的代谢组学变化细节，并显示了在1型糖尿病发生早期检测生化变化的可能性。
