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Objective To study the effects of Apelin on glucose toxicity and islet cells PDX-1 protein expression.Methods The islet β cell line NIT-1 cells were incubated in the medium containing different glucose concentrations(normal glucose concentration group 5.6 mmol/L,high glucose concentration group 16.7 mmol/L,extremely high glucose concentration group 33.3 mmol/L) and +/-Apelin-36 respectively for 3 d.Then the basic insulin secretion amount of islet cells and their secretion amount after glucose stimulation were detected.The intracellular insulin content and the PDX-1 protein and mRNA expression were detected.Results Compared with the normal glucose group,the basic insulin secretion,secretion after stimulation and intracellular insulin in the high glucose group and extremely high glucose group were significantly decreased and PDX-1 protein expression was declined(P＜ 0.05);compared with non-adding Apelin group,the basic insulin secretion,secretion after stimulation and intracellular insulin in the adding Apelin high glucose group and extremely high glucose group were significantly decreased and PDX-1 protein expression was decreased(P＜0.05);the insulin level in islet cells of 6 groups was positively correlated with PDX-1 protein expression and had no correlation with PDX-1 mRNA expression.Conclusion Apelin may participate in the glucose toxic effect by decreasing PDX-1 protein expression,causes the decrease of insulin secretion,thus plays a role in the pathogenesis of diabetes.
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Objective Pancreatic duodenal homeobox-1 ( PDX-1) plays an important role in the occurrence and development of diabetes.More importantly,its potential application in insulin resistance (IR) improvement is attracting further attention .Berberine has been shown to improve glucose metabolism and insulin resistance .In this study,rat models of type 2 diabetes mellitus ( T2DM) were established by combination of intraperitoneal injection of low -dose streptozotocin and highg-lucose-high-fat diet induction .The effect of berberine on fasting glucose , fasting serum insulin , homeostasis model assessment of insulin resistance ( HOMAI-R) , and ex-pression of PDX -1 of islet in T2DM rats were analyzed .The present study aimed to evaluate the anti-diabetic efficacy of berberine and study the mechanism of its preliminary therapeutic effects .Methods Twenty healthy adult male Sprague Dawley ( SD) rats were di-vided by random number table into the normal control group ( n =6) feeding with a standard diet ,and the experimental group ( n =14 ) given an intraperitoneal injection of streptozotocin .The rats with fasting blood glucose ( FBG) greater than 13.8 mmol/L were ran-domly divided into diabetes mellitus group feeding high sugar high fat diet for two weeks and then continuing with a standard diet , and the berberine group given berberine [180 mg /(kg· d)] every day.The normal control group and diabetes mellitus group were given physiological saline for every day 6 weeks.At the end of 6th week, the rats were executed , and the levels of fasting glucose, fasting se-rum insulin, HOMA-IR, and expression of PDX-1 in pancreas islet of each group were detected .The expression of PDX1-in pancreas islet was examined by immunohistochemistry .The image pro plus 6.0software was used to calculate the integrated optical density ( IOD) of positive expression .Results Compared with the normal control group , FBG, fasting insulin levels ( FINS) , and HOMA-IR of the diabetes mellitus group and berberine group were significantly increased ( P <0.05 ) .Compared with the diabetes mellitus group, FBG, FINS, and HOMA-IR of the berberine group were statistically significantly decreased [ ( 13.11 ±6.87 ) mmol/L vs (18.45 ±4.69) mmol L/, (2.58 ±0.34) μIU/ml vs (2.98 ±0.40) μIU/ml, 1.60 ±0.91 vs 2.75 ±0.28, P <0.05].Compared with the normal control group , the expression of PDX-1 of the islet in the diabetes mellitus group and berberine group was statistically significantly decreased ( P <0.05).After treatment with berberine, FBG, FINS, HOMA-IR, and IOD of PDX-1 in pancreas islet of berberine treatment rats were significantly increased compared with the diabetes mellitus group ( 9.14 ±1.51 vs 6.79 ±0.98 , P <0.01 ) .Conclusions The increases of PDX-1 in islet may be one of the mechanism in the improvement of hyperglycemia .
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Objective To determine the coagulation status as well as circulating levels of complement and inflammation markers in patients with chronic urticaria (CU) during acute attack and in remission,and to estimate the relationship of coagulant and anticoagulant factors as well as fibrinolytic markers with the development of chronic urticaira.Methods This study included 40 patients with CU (22 during acute attack and 18 in remission) and 40 healthy blood donors from the Guangzhou Blood Center.Venous blood samples were obtained from these subjects,and enzyme-linked immunosorbent assay (ELISA) was performed to measure the plasma levels of prothrombin fragrnent 1 +2 (F1 +2),tissue factor (TF),thrombomodulin (TM),high molecular weight kininogen (HMWK),tissue-type plasminogen activator (t-PA),C5a and serum levels of C3,C4,antistreptolysin O antibodies (ASO),rheumatoid factor (RF) and C-reactive protein (CRP).Erythrocyte sedimentation rate (ESR) was also determined in these patients.Comparisons of these parameters were carried out by using t test,and the correlation of these factors with CU was evaluated by using Spearman correlation coefficient.Results Compared with the healthy controls,the patients with CU showed significantly higher plasma levels of F1+2 and HMWK (both P ＜ 0.01),but lower levels of TF,TM and t-PA (all P ＜ 0.01).The plasma levels of F1 +2,HMWK,t-PA were significantly correlated with the symptom scores in patients with CU (r =0.81,P ＜ 0.01; r =-0.39,P ＜ 0.05; r =0.35,P ＜ 0.05).A significant increase was observed in the plasma concentration of F1 +2 in patients during acute attack compared with those in remission (P ＜ 0.01),whereas no significant differences were noted in the plasma levels of TF,TM,HMWK,t-PA,C5a,serum levels of C3,C4,ASO,RF and CRP or ESR between the two groups of patients (all P ＞ 0.05).Conclusions It seems that coagulation,anti-coagulation and fibrinolysis are all involved in the development of urticaria.There is an obvious difference in the plasma level of prothrombin F1 +2 between patients with CU during acute attack and in remission,suggesting that coagulation factors play a certain role in the initiation and progression of CU.
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Objective To investigate effect of berberine on fasting glucose , fasting serum insulin, islet morphology, and ex-pression of glucose transporter 4 (GLU-4) of islet in type 2 diabetes mellitus (T2DM) rats.The present study aimed to evaluate the ually, especially for high-dose group ( P <0.01).⑷Compared with normal group , INS of diabetic control group was significantly de-creased ( P <0.05), INS of low-dose, middle-dose, and high-dose groups were all increased gradually , especially for high-dose group ( P <0.01 ) .Conclusions Berberine has the effects of antidiabetes via ameliorate insulin sensitivity , and promotes GLUT-4 protein expression .
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Objective A multicenter, randomized, controlled and open-labled clinical trial was performed to compare the efficacy and safety of recombinant human insulin injection ( Yousilin R) and treated with Yousilin R versus Novolin R for 12 weeks respectively. Results Compared with baseline,the levels of glycosylated hemoglobin A1c ( HbA1c ) at the end of 12 weeks treatment decreased from 10. 77% to 7. 72% ( P ＜0. 05 ) in Yousilin R group and from 10. 33% to 7. 62% ( P ＜0. 05 ) in Novolin R group,2-hour postprandial plasma glucose ( 2hPG ) decreased from 15.49 mmol/L to 9. 72 mmol/L ( P ＜ 0. 05 ) in Yousilin R group and from 15.33 mmol/L to 10. 07 mmol/L( P ＜ 0. 05 ) in Novolin R group, and fasting plasma glucose (FPG) decreased from 10. 90 mmol/L to 7. 31 mmol/L( P ＜0. 05 ) in Yousilin R group and from 10. 22 mmol/L to 7.21 mmol/L (P ＜0. 05) in Novolin R group. The changes of HbA1c, 2hPG and FPG from baseline to endpoint in Yousilin R group was similar to those in Novolin R group ( P ＞ 0. 05 ).Furthermore, hypoglycemic events(26. 42% vs 30. 48% ), other adverse events( 13.21%vs 16. 19% ) ,and serious adverse events( 1.89%vs 1.90% )were comparable between Yousilin R and Novolin R groups(P ＞0. 05 ). Conclusions Yousilin R has similar efficacy, safety and compliance profiles to Novolin R group in the treatment of diabetic patients.
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Objective To study the effects of supra-physiologic glucose on the expression of PDX-1 and insulin secretion. Methods Islet cells isolated from SD rats were incubated in medium containing 5.6 mmol/L or 33 mmol/L glucose respectively for 3 days. Basic and glucose-induced insulin levels in supernate and in islet cells were detected. The PDX-1 mRNA and protein were detected. Results (1) Islet cells exposed to 33 mmol/L vs 5.6 mmol/L glucose for 3 days showed significant decrease in the basic and glucose-induced insulin release, and in cell insulin content and PDX-1 protein. (2) Prolonging incubation of islet cells in 33 mmol/L glucose aggravated the inhibitive effect on PDX-1 expression and insulin secretion. (3)Recovery to normal concentration of glucose in 3 days could partly improve PDX-1 expression and insulin secretion. Conclusions Inhibition of PDX-1 is one of the mechanism of glucotoxicity, and recovery to normal concentration of glucose in 3 days can partly improve PDX-1 expression and insulin secretion.
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In the study of T2DM(n=30),IGR(n=26) and NGT(n=30) cases in Guangxi Province,T2DM had higher resistin and PAI-1 levels than did the groups of IGR and NGT(P<0.05).IGR had higher levels of PAI-1 and leptin than NGT(P<0.05).Leptin level of T2DM was higher than that of NGT(P<0.05).Insulin resistance index was positively correlated with leptin,TG and PAI-1 levels(P<0.05).
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ObjectiveTo determine the primary control factors of nucleotides metabolisms on insulin secretion.MethodsNMRI mice isolated islets were used to investigate the amount of insulin secretion and the changes of ATP,ADP,GTP,GDP and UTP in islets when the activity of K+ATP channel was eliminated by diazoxide.ResultsThe above assays demonstrated that insulin secretion increased with the rise of glucose concentration.In the same time,ratio of ATP/ADP,GTP/GDP and level of UTP increased,too.All three indexes correlated with the insulin secretion very well respectively,but only ratio of ATP/ADP can control insulin secretion directly in common influence.ConclusionOur findings suggest that there is the second control site in islets when glucose induces insulin secretion and ATP/ADP ratio is only key factor in this mechanism.
