Systematic assessment of streptozotocin-induced diabetic metabolic alterations in rats using metabolomics

Abstract

PurposeType 1 diabetes is characterized by elevated blood glucose levels, which negatively impacts multiple organs and tissues throughout the body, and its prevalence is on the rise. Prior reports primarily investigated the serum and urine specimen from diabetic patients. However, only a few studies examined the overall metabolic profile of diabetic animals or patients. The current systemic investigation will benefit the knowledge of STZ-based type 1 diabetes pathogenesis.MethodsMale SD rats were arbitrarily separated into control and streptozotocin (STZ)-treated diabetic rats (n = 7). The experimental rats received 50mg/kg STZ intraperitoneal injection daily for 2 consecutive days. Following 6 weeks, metabolites were assessed via gas chromatography-mass spectrometry (GC-MS), and multivariate analysis was employed to screen for differentially expressed (DE) metabolites between the induced diabetic and normal rats.ResultsWe identified 18, 30, 6, 24, 34, 27, 27 and 12 DE metabolites in the serum, heart, liver, kidney, cortex, renal lipid, hippocampus, and brown fat tissues of STZ-treated diabetic rats, compared to control rats. Based on our analysis, the largest differences were observed in the amino acids (AAs), B-group vitamin, and purine profiles. Using the metabolic pathway analysis, we screened 13 metabolic pathways related to the STZ-exposed diabetes pathogenesis. These pathways were primarily AA metabolism, followed by organic acids, sugars, and lipid metabolism.ConclusionBased on our GC-MS analysis, we identified potential metabolic alterations within the STZ-exposed diabetic rats, which may aid in the understanding of diabetes pathogenesis.