Systemic and characteristic metabolites in the serum of streptozotocin-induced diabetic rats at different stages as revealed by a (1)H-NMR based metabonomic approach.

Diabetes mellitus is a typical heterogeneous metabolic disorder characterized by abnormal metabolism of carbohydrates, lipids, and proteins. Investigating the changes in metabolic pathways during the evolution of diabetes mellitus may contribute to the understanding of its metabolic features and pathogenesis. In this study, serum samples were collected from diabetic rats and age-matched controls at different time points: 1 and 9 weeks after streptozotocin (STZ) treatment. (1)H nuclear magnetic resonance ((1)H NMR)-based metabonomics with quantitative analysis was performed to study the metabolic changes. The serum samples were also subjected to clinical chemistry analysis to verify the metabolic changes observed by metabonomics. Partial least squares discriminant analysis (PLS-DA) demonstrated that the levels of serum metabolites in diabetic rats are different from those in control rats. These findings indicate that the metabolic characteristics of the two groups are markedly different at 1 and 9 weeks. Quantitative analysis showed that the levels of some metabolites, such as pyruvate, lactate, citrate, acetone, acetoacetate, acetate, glycerol, and valine, varied in a time-dependent manner in diabetic rats. These results suggest that serum metabolites related to glycolysis, the tricarboxylic acid cycle, gluconeogenesis, fatty acid ß-oxidation, branched-chain amino acid metabolism, and the tyrosine metabolic pathways are involved in the evolution of diabetes. The metabolic changes represent potential features and promote a better understanding of the mechanisms involved in the development of diabetes mellitus. This work further suggests that (1)H NMR metabonomics is a valuable approach for providing novel insights into the pathogenesis of diabetes mellitus and its complications.

Systemic perturbations of key metabolites in diabetic rats during the evolution of diabetes studied by urine metabonomics.

BACKGROUND: Elucidation of metabolic profiles during diabetes progression helps understand the pathogenesis of diabetes mellitus. In this study, urine metabonomics was used to identify time-related metabolic changes that occur during the development of diabetes mellitus and characterize the biochemical process of diabetes on a systemic, metabolic level. METHODOLOGY/PRINCIPAL FINDINGS: Urine samples were collected from diabetic rats and age-matched controls at different time points: 1, 5, 10, and 15 weeks after diabetes modeling. (1)H nuclear magnetic resonance ((1)H NMR) spectra of the urine samples were obtained and analyzed by multivariate data analysis and quantitative statistical analysis. The metabolic patterns of diabetic groups are separated from the controls at each time point, suggesting that the metabolic profiles of diabetic rats were markedly different from the controls. Moreover, the samples from the diabetic 1-wk group are closely associated, whereas those of the diabetic 15-wk group are scattered, suggesting that the presence of various of complications contributes significantly to the pathogenesis of diabetes. Quantitative analysis indicated that urinary metabolites related to energy metabolism, tricarboxylic acid (TCA) cycle, and methylamine metabolism are involved in the evolution of diabetes. CONCLUSIONS/SIGNIFICANCE: The results highlighted that the numbers of metabolic changes were related to diabetes progression, and the perturbed metabolites represent potential metabolic biomarkers and provide clues that can elucidate the mechanisms underlying the generation and development of diabetes as well as its complication.

Improved refractory wound healing with administration of acidic fibroblast growth factor in diabetic rats.

The aim of the present study is to investigate the effect and mechanism of acidic fibroblast growth factor (aFGF) on treating refractory wound of diabetic rats. SD rats were randomly divided into control group, diabetes group, and aFGF group. Ulcer skin tissues of three groups of rats were respectively collected on days 7 and 14 after establishment of ulcer model for biochemical test, pathological section and immunohistochemistry to comprehensively evaluate the treatment effect of aFGF on diabetic ulcer. The results showed that aFGF could significantly increase capillaries and fibroblast amounts of ulcer tissues, enhance the expression of TGF-ß and PCNA proliferation proteins, and thus improved diabetic ulcer tissues. The preliminary mechanism that aFGF helps to promote healing of diabetic ulcer is possibly associated with that aFGF stimulated ulcer skins to secrete TGF-ß and PCNA proteins and promoted proliferation of capillaries and fibroblasts.