Streptozotocin-induced dynamic metabonomic changes in rat biofluids

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 ¹H 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.