Abstract:Type 2 diabetes (T2DM) is a multi-factorial disease with a complex pathogenic mechanism; however a complete understanding of precise biochemical alterations accompanying the onset and progression of T2DM is lacking. Using a combination of untargeted and targeted metabolomic profiling approach we were able to delineate significantly altered metabolites in the diabetic (T2DM) group. Our results indicate significant perturbations in amino acid metabolism, TCA cycle and glycerol-phospholipid metabolism possibly im… Show more
“…DM also results in aberrant amino acid metabolism35. In this study, the DM rats had significantly lower serum glycine, glutamine, histidine, phenylalanine and tyrosine levels than the normal rats, whereas their levels were significantly increased by bFGF treatment.…”
The fibroblast growth factors (FGFs) family shows a great potential in the treatment of diabetes, but little attention is paid to basic FGF (bFGF). In this study, to explore the metabolic effects of bFGF on diabetes, metabolic changes in serum and feces were analyzed in the normal rats, the streptozocin (STZ)-induced diabetic rats and the bFGF-treated diabetic rats using a 1H nuclear magnetic resonance (NMR)-based metabolomic approach. Interestingly, bFGF treatment significantly decreased glucose, lipid and low density lipoprotein/very low density lipoprotein (LDL/VLDL) levels in serum of diabetic rats. Moreover, bFGF treatment corrected diabetes-induced reductions in citrate, lactate, choline, glycine, creatine, histidine, phenylalanine, tyrosine and glutamine in serum. Fecal propionate was significantly increased after bFGF treatment. Correlation analysis shows that glucose, lipid and LDL/VLDL were significantly negatively correlated with energy metabolites (citrate, creatine and lactate) and amino acids (alanine, glycine, histidine, phenylalanine, tyrosine and glutamine). In addition, a weak but significant correlation was observed between fecal propionate and serum lipid (R = −0.35, P = 0.046). Based on metabolic correlation and pathway analysis, therefore, we suggest that the glucose and lipid lowering effects of bFGF in the STZ-induced diabetic rats may be achieved by activating microbial metabolism, increasing energy metabolism and correcting amino acid metabolism.
“…DM also results in aberrant amino acid metabolism35. In this study, the DM rats had significantly lower serum glycine, glutamine, histidine, phenylalanine and tyrosine levels than the normal rats, whereas their levels were significantly increased by bFGF treatment.…”
The fibroblast growth factors (FGFs) family shows a great potential in the treatment of diabetes, but little attention is paid to basic FGF (bFGF). In this study, to explore the metabolic effects of bFGF on diabetes, metabolic changes in serum and feces were analyzed in the normal rats, the streptozocin (STZ)-induced diabetic rats and the bFGF-treated diabetic rats using a 1H nuclear magnetic resonance (NMR)-based metabolomic approach. Interestingly, bFGF treatment significantly decreased glucose, lipid and low density lipoprotein/very low density lipoprotein (LDL/VLDL) levels in serum of diabetic rats. Moreover, bFGF treatment corrected diabetes-induced reductions in citrate, lactate, choline, glycine, creatine, histidine, phenylalanine, tyrosine and glutamine in serum. Fecal propionate was significantly increased after bFGF treatment. Correlation analysis shows that glucose, lipid and LDL/VLDL were significantly negatively correlated with energy metabolites (citrate, creatine and lactate) and amino acids (alanine, glycine, histidine, phenylalanine, tyrosine and glutamine). In addition, a weak but significant correlation was observed between fecal propionate and serum lipid (R = −0.35, P = 0.046). Based on metabolic correlation and pathway analysis, therefore, we suggest that the glucose and lipid lowering effects of bFGF in the STZ-induced diabetic rats may be achieved by activating microbial metabolism, increasing energy metabolism and correcting amino acid metabolism.
“…Defects in the mitochondrial respiratory chain and mitochondrial dysfunction as a significant factor in insulin resistance induced by fatty acids and type 2 diabetes is one of the critical areas in metabolic disorders, which is growing in importance [35]. We found an increase in pyruvate levels in plasma, which has been reported in patients with type 2 diabetes [36]. Furthermore, hyperglycemia might also boost the rate of glucose oxidation towards the excessive formation of pyruvate, indicating that the metabolic adaptations are directed to glycolytic pathways in the progression towards type 2 diabetes and insulin resistance [35].…”
Metabolic syndrome (MetS) has become one of the main concerns for public health because of its link to cardiovascular disease. Murine models have been used to study the effect of MetS on the cardiovascular system, but they have limitations for studying cardiac electrophysiology. In contrast, the rabbit cardiac electrophysiology is similar to human, but a detailed characterization of the different components of MetS in this animal is still needed. Our objective was to develop and characterize a diet-induced experimental model of MetS that allows the study of cardiovascular remodeling and arrhythmogenesis. Male NZW rabbits were assigned to control (n = 15) or MetS group (n = 16), fed during 28 weeks with high-fat, high-sucrose diet. We measured weight, morphological characteristics, blood pressure, glycaemia, standard plasma biochemistry and the metabolomic profile at weeks 14 and 28. Liver histological changes were evaluated using hematoxylin-eosin staining. A mixed model ANOVA or unpaired t-test were used for statistical analysis (P<0.05). Weight, abdominal contour, body mass index, systolic, diastolic and mean arterial pressure increased in the MetS group at weeks 14 and 28. Glucose, triglycerides, LDL, GOT-AST, GOT/GPT, bilirubin and bile acid increased, whereas HDL decreased in the MetS group at weeks 14 and 28. We found a 40% increase in hepatocyte area and lipid vacuoles infiltration in the liver from MetS rabbits. Metabolomic analysis revealed differences in metabolites related to fatty acids, energetic metabolism and microbiota, compounds linked with cardiovascular disease. Administration of high-fat and high-sucrose diet during 28 weeks induced obesity, glucose intolerance, hypertension, non-alcoholic hepatic steatosis and metabolic alterations, thus reproducing the main clinical manifestations of the metabolic syndrome in humans. This experimental model should provide a valuable tool for studies into the mechanisms of cardiovascular problems related to MetS, with special relevance in the study of cardiovascular remodeling, arrhythmias and SCD.
“…6A). Both pyruvate and L-serine are present in human and murine urine, and levels are elevated in diabetic populations 21–23 . Given that BtsS/BtsR responds directly to extracellular pyruvate levels and indirectly to L-serine, we asked whether BtsS/BtsR is active in the bladder lumen during acute and chronic UTI.Figure 6BtsS/BtsR importance during urinary tract infection.…”
Two-component systems are crucial for signal perception and modulation of bacterial behavior. Nevertheless, to date, very few ligands have been identified that directly interact with histidine kinases. The histidine kinase/response regulator system YehU/YehT of Escherichia coli is part of a nutrient-sensing network. Here we demonstrate that this system senses the onset of nutrient limitation in amino acid rich media and responds to extracellular pyruvate. Binding of radiolabeled pyruvate was found for full-length YehU in right-side-out membrane vesicles as well as for a truncated, membrane-integrated variant, confirming that YehU is a high-affinity receptor for extracellular pyruvate. Therefore we propose to rename YehU/YehT as BtsS/BtsR, after “Brenztraubensäure”, the name given to pyruvic acid when it was first synthesized. The function of BtsS/BtsR was also assessed in a clinically relevant uropathogenic E. coli strain. Quantitative transcriptional analysis revealed BtsS/BtsR importance during acute and chronic urinary-tract infections.
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