Abstract
Background High levels of branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) were associated with an increased risk of hyperglycemia and the onset of diabetes. This study is aimed at assessing circulating valine concentrations in subjects with type 2 diabetes (T2D) and in T2D patients and high-fat diet- (HFD-) fed mice treated with the hypoglycemic agent sitagliptin (Sit) and analyzing the association of valine concentrations with metabolic parameters. Methods Metabolomics in HFD-fed mice were analyzed by gas chromatography-mass spectrometry (GC-MS) systems. Plasma valine concentrations were detected with a commercial kit in 53 subjects with normal glucose levels (n = 19), newly diagnosed T2D (n = 20), placebo-treated T2D (n = 7), or Sit-treated T2D (n = 7). Biochemical parameters were also assessed in all participants. Results Sit treatment markedly changed the pattern of amino acid in HFD-fed mice, especially by reducing the level of the BCAA valine. Compared with the healthy controls, the plasma valine concentrations were significantly higher in the T2D patients (p < 0.05). Correlation analysis showed that the plasma valine concentration was positively correlated with the level of fasting plasma glucose (p < 0.05). Moreover, the plasma valine concentrations were notably reduced after Sit treatment in T2D patients (p < 0.05). Conclusions Our findings demonstrate an important effect of Sit on the BCAA valine in T2D patients and HFD-fed mice, revealing a new hypoglycemic mechanism of it. Furthermore, the results suggest that the circulating valine level might be a novel biomarker for T2D and restoring the level of valine might be a potential strategy for diabetes therapy.
Highlights
The intestinal gut microbiota is an intricate ecosystem
We demonstrated that metabolites were markedly changed after Sit treatment in high-fat diet- (HFD-)fed mice [9]
To further explore the alterations of amino acids induced by Sit treatment in high fat diet (HFD)-fed mice, principal component analysis (PCA) and heat map analysis were performed based on the amino acid concentrations detected by GCMS
Summary
The intestinal gut microbiota is an intricate ecosystem. Existing evidence has indicated that the gut microbiota is involved in regulating the homeostasis of the host metabolism [1]. Our recent study reported that the commonly used oral hypoglycemic agent, dipeptidyl peptidase-4 inhibitors (DPP-4i), markedly changed the composition of the gut Mediators of Inflammation microbiota and the pattern of metabolites in high-fat diet(HFD-) fed mice and that the DPP-4i sitagliptin- (Sit-) altered microbiome from type 2 diabetes (T2D) patients improved the glucose intolerance induced by HFD in germ-free mice [9]. This study is aimed at assessing circulating valine concentrations in subjects with type 2 diabetes (T2D) and in T2D patients and high-fat diet- (HFD-) fed mice treated with the hypoglycemic agent sitagliptin (Sit) and analyzing the association of valine concentrations with metabolic parameters. Sit treatment markedly changed the pattern of amino acid in HFD-fed mice, especially by reducing the level of the BCAA valine. The results suggest that the circulating valine level might be a novel biomarker for T2D and restoring the level of valine might be a potential strategy for diabetes therapy
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