Glucagon-like peptide-1 improves proliferation and differentiation of endothelial progenitor cells via upregulating VEGF generation.

BACKGROUND: Glucagon-like peptide-1(GLP-1), released from enteroendocrine cells of the intestine, exerted cardiovascular protective effect. Circulating endothelial progenitor cells (EPCs) play an important role in maintaining endothelial integrity regulating neovascularization and reendothelialization after endothelial injury. Vascular endothelial growth factor (VEGF) is an important cytokine in the process of EPCs vascular differentiation and proliferation. MATERIAL/METHODS: This study was designed to investigate the association between VEGF changes and the proliferation/differentiation function of EPCs in the presence of GLP-1. RESULTS: We demonstrated that GLP-1 markedly enhanced the EPCs proliferation and expression of EC-specific markers, and simultaneously upregulated VEGF secretion in EPCs. Exogenous VEGF augmented EPCs proliferation/differentiation abilities in a dose-dependent manner. However, all of the beneficial effects of GLP-1were suppressed by anti-VEGFmAb or the KDR-specific tyrosine kinase inhibitor SU1498. CONCLUSIONS: These findings suggest that GLP-1 improves VEGF generation, which contributed to improvement of EPCs biological function, partly by tyrosine kinase KDR. VEGF is a necessary intermediate, mediating the effects of GLP-1 on EPCs. These changes offer a novel explanation that upregulation EPCs bioactivities may be one of the mechanisms of GLP-1 cardiovascular protective effect.

Effect of repaglinide and gliclazide on glycaemic control, early-phase insulin secretion and lipid profiles in / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Both repaglinide and gliclazide are insulin secretagogues widely used in the treatment of type 2 diabetes. They stimulate insulin secretion through distinct mechanisms and may benefit patients from different aspects. The present study was to evaluate the effects of repaglinide or gliclazide on glycaemic control, insulin secretion, and lipid profiles in type 2 diabetes patients.</p><p><b>METHODS</b>A total of 47 newly diagnosed type 2 diabetes patients were randomized 1:1 to receive a 4-week treatment with repaglinide or gliclazide. The standard mixed meal tolerance test was performed before and after the treatment. Plasma glucose (PG), insulin concentration, and lipid profiles were measured. The area under insulin concentration curve (AUC(ins)) and the early-phase insulin secretion index (ΔI(30)/ΔG(30)) were calculated.</p><p><b>RESULTS</b>After the trial, fasting and postprandial PG and postprandial insulin improved significantly in both groups (P < 0.05). The maximum insulin concentration occurred earlier in the repaglinide group than that in the gliclazide group. AUC(ins) increased in both groups (P < 0.05), but no significant difference was found between groups. ΔI(30)/ΔG(30) increased in both groups (P < 0.05), especially in the repaglinide group (P < 0.05). Triglyceride and total cholesterol decreased significantly in the repaglinide group in some time points, while no significant change was observed in the gliclazide group.</p><p><b>CONCLUSIONS</b>Repaglinide and gliclazide had similar effects on glycaemic control and total insulin secretion, while repaglinide had more effects on improvements in β-cell function and lipid metabolism.</p>

Effect of different glucose concentrations on the expressions of insig-1 and insig-2 mRNA during the differentiation of 3T3-L1 cells / 中南大学学报(医学版)

OBJECTIVE@#To determine the effect of different concentrations of glucose on the differentiation of 3T3-L(1) and the expression of insig-1 and insig-2 mRNA, and to explore the effect of insulin-induced gene in the differentiation and formation of adipocytes and lipogenesis.@*METHODS@#The 3T3-L(1) cells were induced to differentiate in high glucose concentration (25 mol/L G.S), low glucose concentration (5.5 mol/L G.S), and mannitol (19.5 mol/L Mannitol +5.5 mol/L G.S), respectively. The differentiation of 3T3-L(1) cells was examined by oil red "O" straining, and the expression of insig-1,insig-2 mRNA and AP2 mRNA was examined by RT-PCR and in situ hybridization.@*RESULTS@#With the differentiation of 3T3-L(1) cells, the expression of insig-1 and insig-2 mRNA was gradually up-regulated. The expression of insig-1 and insig-2 mRNA significantly increased while AP(2) mRNA decreased in the low glucose concentration inducing group and mannitol inducing group. In the high glucose concentration inducing group, the cell differentiation was poor (P<0.05). There was no difference between the low glucose concentration and the mannitol group in the differentiation of 3T3-L(1) cells, and in the expression of insig-1 and insig-2 and AP(2) mRNA.@*CONCLUSION@#Different concentrations of glucose may influence the cell differentiation and the low glucose concentration promotes insig-1 and insig-2 gene expression, which may lead to the inhibition of the differentiation and lipogenesis of preadipocytes.

Effect of sodium tungstate on glucose metabolism in adipocytes / 中南大学学报(医学版)

OBJECTIVE@#To explore the effect of sodium tungstate on glucose metabolism in adipocytes and its mechanism.@*METHODS@#After 3T3-L1 preadipocytes were differentiated into adipocytes, these adipocytes were incubated with sodium tungstate (0, 150, 300, 500, and 700 micromol/L) for 48 h, and then glucose consumption of the adipocytes was detected by glucose-oxidase assay. Glucose transport was determined by the uptake of 2-deoxy-[3H]-D-glucose, and the expression of glucose transport-4 (GLUT-4) mRNA was identified by semi-quantitative RT-PCR.@*RESULTS@#Sodium tungstate (150 approximately 700 micromol/L) could significantly increase the glucose consumption and glucose transport with a concentration dependent-effect. Sodium tungstate could increase GLUT-4 mRNA expression.@*CONCLUSION@#Sodium tungstate can enhance the glucose metabolism of adipocytes by up-regulating the expression of GLUT-4 mRNA.

Expression of hCTLA4-Ig mediated by adeno-associated virus in porcine islets and their biological activity / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the expression of hCTLA4-Ig and their biological function in newborn porcine islets (NPIs) transfected with AAV-hCTLA4-Ig.@*METHODS@#Cultured NPIs were transfected with AAV-hCTLA4-Ig. The expression of CTLA4-Ig in these NPIs was assayed by RT-PCR and immunocytochemistry. The levels of IL-2, IFN-gamma, and TNF-alpha in the culture medium were assayed by ELISA after these cells the co-cultured with human. The response of glucose-stimulated insulin secretion was observed in the transgene group and the control group.@*RESULTS@#The expressions of CTLA4-Ig mRNA and protein were detected in the transgene group. The levels of cytokines were obviously lower in the transgene group than those in the control group (P0.05).@*CONCLUSION@#AAV mediated hCTLA4-Ig expression in NPIs could inhibit T lymphocyte to produce cytokines, while the endocrine functions of the NPIs were not significantly affected.

Porcine endogenous retrovirus in Daweizi pigs in Hunan / 中南大学学报(医学版)

OBJECTIVE@#To detect porcine endogenous retrovirus (PERV) in Daweizi pigs and to provide basic parameters of evaluating the biological safety for xenotransplantation from pigs to humans.@*METHODS@#Ear tissues from 42 individuals were randomly collected from a Daweizi pig population. PCR and RT-PCR were performed to detect PERV proviral DNA and mRNA respectively. Finally, env-A, env-B, and env-C were amplified, sequenced, and analyzed using the BLAST software in National Center for Biotechnology Information.@*RESULTS@#PERV proviral DNA and mRNA could be detected in the 42 individuals by PCR and RT-PCR, respectively. env-A, env-B and env-C were detected in all the individuals. Compared with other pig species (AY288779, DQ011794 and AY534304), there was 1 and 8 bp differences in the sequences of env-A and env-C, while no difference in env-B.@*CONCLUSION@#PERV exists and has transcriptive activity in Daweizi pigs. The predominate subtype is PERV-ABC. Env genes are firstly cloned and sequenced in Daweizi pigs and there are polymorphism in the breed. As to the biological safety, the breed was not suitable as a donor in xenotransplantation.