ABSTRACT
BACKGROUND: Diabetes is a clinically common chronic disease, and its incidence has been increasing in recent years. Diabetes is believed to accelerate the process of atherosclerosis in patients, and abnormal endothelial function is an important factor leading to diabetic kidney damage. AIM: To investigate the efficacy of ligliptin in the treatment of type 2 diabetes mellitus (T2DM) with early renal injury and its effect on serum endogenous hydrogen sulfide (H2S), endothelial cell particles, and endothelial function. METHODS: From January 2018 to April 2019, 110 patients with T2DM and early kidney injury treated at our hospital were divided into an observation group (receiving ligliptin treatment, n = 54) and a control group (receiving gliquidone therapy, n = 56). Blood glucose and renal function before and after treatment were compared between the two groups. RESULTS: The differences in fasting blood glucose, 2 h blood glucose, and glycated hemoglobin were not statistically significant between the two groups after treatment. The urinary albumin excretion rate after treatment in the ligliptin group was 70.32 ± 11.21 µg/min, which was significantly lower than that of the gliquidone group (P = 0.000). Serum endogenous H2S and endothelial cell microparticles of the ligliptin treatment group were 40.04 ± 8.82 mol/L and 133.40 ± 34.39, respectively, which were significantly lower than those of the gliquidone treatment group (P = 0.000 for both); endothelin-dependent diastolic function and nitric oxide after treatment in the ligliptin group were 7.98% ± 1.22% and 190.78 ± 30.32 mol/L, significantly higher than those of the gliquidone treatment group (P = 0.000 for both). CONCLUSION: Ligliptin treatment of T2DM with early renal injury has the same glucose-lowering effect as gliquidone treatment. Ligliptin treatment has a better effect and it can significantly improve the renal function and vascular endothelial function of patients, and reduce serum endogenous H2S and endothelial cell particle levels.
ABSTRACT
Chlorogenic acid (CGA), abundant in coffee and particular fruits, can modulate hypertension and vascular dysfunction. Hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) proliferation has been tightly linked to vascular remodeling in pulmonary arterial hypertension (PAH). Thus, the present study was designed to investigate the effect of CGA on hypoxia-induced proliferation in cultured rat PASMCs. The data showed that CGA potently inhibited PASMCs proliferation and DNA synthesis induced by hypoxia. These inhibitory effects were associated with G1 cell cycle arrest and down-regulation of cell cycle proteins. Treatment with CGA reduced hypoxia-induced hypoxia inducible factor 1α (HIF-1α) expression and trans-activation. Furthermore, hypoxia-evoked c-Src phosphorylation was inhibited by CGA. In vitro ELISA-based tyrosine kinase assay indicated that CGA was a direct inhibitor of c-Src. Moreover, CGA attenuated physical co-association of c-Src/Shc/Grb2 and ERK2 phosphorylation in PASMCs. These results suggest that CGA inhibits hypoxia-induced proliferation in PASMCs via regulating c-Src-mediated signaling pathway. In vivo investigation showed that chronic CGA treatment inhibits monocrotaline-induced PAH in rats. These findings presented here highlight the possible therapeutic use of CGA in hypoxia-related PAH.
Subject(s)
Chlorogenic Acid/pharmacology , MAP Kinase Signaling System/drug effects , Muscle, Smooth, Vascular/cytology , Protein Kinase Inhibitors/pharmacology , Pulmonary Artery/cytology , Animals , CSK Tyrosine-Protein Kinase , Cell Cycle Proteins/genetics , Cell Hypoxia/drug effects , Cell Proliferation/drug effects , Chlorogenic Acid/therapeutic use , DNA/biosynthesis , Down-Regulation/drug effects , G1 Phase/drug effects , GRB2 Adaptor Protein/metabolism , Hypertension, Pulmonary/chemically induced , Hypertension, Pulmonary/drug therapy , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Male , Mitogen-Activated Protein Kinase 1/metabolism , Monocrotaline/adverse effects , Muscle, Smooth, Vascular/metabolism , Phosphorylation/drug effects , Protein Kinase Inhibitors/therapeutic use , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Transcription, Genetic/drug effects , Transcriptional Activation/drug effects , src-Family Kinases/antagonists & inhibitors , src-Family Kinases/metabolismABSTRACT
Fermented soybean foods have been shown to reduce incidence of diabetes and improve insulin sensitivity. 6-Hydroxydaidzein (6-HD) is a bioactive ingredient isolated from fermented soybean. In this study, we examined the effects of 6-HD on adipocyte differentiation and insulin-stimulated glucose uptake, as well as the mechanisms involved. In our experiments, 6-HD enhanced 3T3-L1 adipocyte differentiation and insulin-stimulated glucose uptake in a dosage-dependent manner. In addition, 6-HD increased peroxisome proliferator-activated receptor gamma (PPARγ) gene expression and PPARγ transcriptional activity. 6-HD increased CCAAT/enhanced binding protein alpha (C/EBPα) expression as well. Although having no effects on glucose transporter type 4 (GLUT4) gene expression, 6-HD facilitated GLUT4 protein translocation to the cell membranes. Our results indicate that 6-HD exhibited the actions of promoting adipocyte differentiation and improving insulin sensitivity by increasing the expression of C/EBPα and facilitating the translocation of GLUT4 via the activation of PPARγ, suggesting that 6-HD can be promising in diabetes management.
