Diabetes mellitus is a complex metabolic disorder characterized by chronic hyperglycemia, hypoinsulinemia, and ketosis. 1 The World Health Organization estimates that by the year 2030, there will be 366 million diabetics worldwide.2 This epidemic is also expected to trigger a steep rise in diabetic complications, such as cardiomyopathy, encephalopathy, and nephropathy. Type 1 diabetes is a T cell-mediated autoimmune disease. 3 The streptozotocin (STZ)-induced rat model is a model of type 1 diabetes associated with a marked decrease in insulin levels, exhibiting metabolic characteristic similar to type 1 diabetes in humans. 4 As a systemic metabolic disease, diabetes mellitus affects multiple organs and tissues throughout the body. 5 In diabetic rats, due to limited glucose utilization, glucokinase activity is essentially lacking in the liver, 6 while glucose transport 7,8 and some key enzymes, including hexokinase, 9 phosphofructokinase, 9 and pyruvate kinase, 10 are reduced in the muscle and multiple organs. Furthermore, the impairment of insulin function augments lipolysis and the release of free fatty acids (FFA) from adipose tissue. 11 The alteration of glucose metabolism facilitates profound disturbances in lipid, amino acid and energy metabolism. Previous work has indicated a pronounced increase of energy expenditure and protein breakdown in type 1 diabetic patients, and also shown that insulin treatment can reduce these processes.
12However, the metabolic profiles involved in the pathological processes of diabetes remain to be addressed.NMR-based metabonomics is a novel approach for rapidly identifying the changes in global metabolite profiles of biological samples and is widely used in disease 13 and biochemical studies.14 Due to its usefulness in evaluating systemic responses to any subtle metabolic perturbation, metabonomics has been used for the diagnosis and evaluation of diabetic patients, 15 and for the identification of potential biomarkers. 16,17 Mäkinen et al. has demonstrated that metabonomic analysis is a highly sensitive and specific approach for diagnosing diabetic nephropathy.18 Additionally, they also developed an effective metabonomic protocol for identificating of a "polydiagnostic metabolite manifold of type 1 diabetes", which allows for the translation of metabolic disturbances tangible, clinical presentations. 19 Recently, Zhang et al. reported a 1 H NMR-based metabonomic analysis of the metabolic changes in urine samples from type 1 diabetic rats induced by STZ, and identified several alterations in metabolic pathways. 20 The integration of metabolic data derived from serum, urine and related tissues could provide a systemic approach for the study of metabolic profiles associated with diabetes and facilitate a detailed examination of the molecular mechanisms underlying this disease.In the present work, we performed NMR-based metabonomic analysis on urine, serum, and liver tissue extracts obtained from STZ-induced type 1 diabetic rats. We sought to determine (i) if we could define the...