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Objective:To explore the role and mechanism of exogenous active peptide spexin in regulating insulin resistance in adipose tissue.Methods:High-fat diet induced obesity model(DIO) mice and diabetic model(db/db) mice were given intraperitoneal injection of spexin(50 μg/kg) for 3 consecutive weeks, while each control group was given an equal volume of saline. After the intervention, the body weight, visceral fat weight and plasma biochemical indexes of the mice in each group were analyzed. Real-time fluorescence quantitative PCR was used to detect mRNA levels of Krüppel-like transcription factor 9(KLF9), peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α) and glucose transporter 4(GLUT4); Western blotting was used to detect the protein levels of KLF9, PGC-1α, GLUT4 and p-p38/p38 in adipose tissue.Results:Compared with DIO control mice, spexin-treated DIO mice showed a significant reduction in body weight ( P=0.043), adiposity ( P<0.001), glucose ( P<0.001), insulin ( P=0.008), HOMA-IR ( P<0.001) and elevation in glucose tolerance ( P=0.006) and insulin tolerance levels ( P=0.002). Compared with db/db control mice, spexin-treated db/db mice showed a significant reduction in body weight ( P<0.001), adiposity ( P<0.001), glucose ( P=0.041), insulin ( P=0.009), HOMA-IR ( P=0.007) and elevation in glucose tolerance ( P=0.008) and insulin tolerance levels ( P=0.031). In addition, the gene and protein levels of KLF9, PGC-1α and GLUT4 were significantly increased in the adipose tissue of spexin-treated DIO mice compared with DIO control mice [genes ( P<0.001, P<0.001, P=0.005); proteins ( P=0.047, P=0.022, P=0.001)], while p-p38/p38 protein levels were significantly decreased in the adipose tissue of spexin-treated DIO mice compared with DIO control mice ( P=0.002). Moreover, the gene and protein levels of KLF9, PGC-1α and GLUT4 were significantly increased in the adipose tissue of spexin-treated db/db mice compared with db/db control mice [genes ( P<0.001, P<0.001, and P=0.005); proteins ( P=0.001, P=0.004, and P<0.001)], while p-p38/p38 protein levels were significantly decreased in the adipose tissue of spexin-treated db/db mice compared with db/db control mice ( P=0.001). Conclusion:These results suggested that spexin may play a role in ameliorating adipose tissue insulin resistance in DIO mice and db/db mice through regulating p38MAPK-mediated inflammation and KLF9-PGC-1α-GLUT4 pathway-mediated glucose uptake.
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Objective@#To explore the inhibitory effect of exosomes secreted by human umbilical cord mesenchymal stem cells(HUCMSC) on apoptosis of human umbilical vein endothelial cells(HUVEC) after model group(oxygen-glucose deprivation reoxygenation), and to clarify its possible mechanism.@*Methods@#Human umbilical cord mesenchymal stem cells were cultured. The collected cell supernatant was stored in a centrifugal tube. The exosomes secreted by human umbilical cord mesenchymal stem cells were extracted by ultracentrifugation and identified. Human umbilical vein endothelial cells were randomly divided into control group, model group and different concentrations of HUCMSC-EXO(20 μg/ml, 40 μg/ml, 60 μg/ml) treatment groups(adding HUCMSC-EXO into the model group) . The morphological changes of HUVEC cells in each group were observed by inverted phase contrast microscope, and the proliferation inhibition rate of HUVEC in each group was measured by CCK-8 reagent. Western blot was used to detect the expression of apoptosis-related proteins Caspase-3, Bax, Bcl-2 and hypoxia-associated protein hypoxia inducible factor 1α(HIF-1α). Inhibitor(HIF-1α inhibitor) + model group and HUCMSC-EXO + inhibitor + model group were added on the basis of the above experiments. Western blot analysis was performed to observe the effects of HUCMSC-EXO, inhibitor and both of them on HIF-1α and Bax expressions in HUVEC.@*Results@#HUCMSC-EXO was successfully extracted and identified. Compared with the control group, the volume of HUVEC in the model group and the HUCMSC-EXO group with different concentrations decreased, became round, connected and evacuated, and the growth state was poor under the inverted phase contrast microscope.CCK-8 detection showed that the cell viability in the HUCMSC-EXO group was significantly higher than that in the model group, the difference was statistically significant (t=9.23, P<0.05). Western blot analysis showed that compared with the control group, the expression levels of Caspase-3 ((0.296±0.038), (0.879±0.088); t=14.92, P<0.05), Bax((0.234±0.034), (0.762±0.084); t=14.36, P<0.05) of HUVEC in the model group were up-regulated, and the expression level of Bcl-2 was down-regulated ((0.863±0.103), (0.387±0.059); t=9.85, P<0.05), with statistically significant differences. Compared with the model group, the expression levels of Caspase-3( (0.586±0.075); t=6.24, P<0.05), Bax((0.311±0.055); t=11.01, P<0.05) and Bcl-2((0.665±0.071); t=7.45, P<0.05) of HUVEC in the HUCMSC-EXO treatment group were down-regulated and the differences were statistically significant. Inhibitor intervention experiments showed that there were no significant differences between the inhibitor+ model group and HUCMSC-EXO+ inhibitor+ model group in the expression of HIF-1α protein ((0.348±0.055), (0.388±0.077); t=1.04, P>0.05)and Bax protein ((0.363±0.069), (0.370±0.064); t=0.18, P>0.05). But both of them were down-regulated compared with the model group (HIF-1α protein (0.919±0.064), Bax protein (0.902±0.071)), the differences were significant( t=13.56, t=13.03, both P<0.05).@*Conclusion@#HUCMSC-EXO has a protective effect on OGD/R model of HUVEC, and its mechanism may be related to the down-regulation of HIF-1α expression.
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Objective To explore the relation of fat cells factor and insulin resistance in type 2 diabetes.Methods 60 patients were divided into obesity group, non-obese group and normal control group.To detect the FINs, FPG, TG, TC, LDL,HDL,APN,CTRP3,leptin and TNF-α, according to the formula of HOMA,to analyze the correlation between indicators.Results 1).Compared with normal control group, DM group significantly decrease serum APN, CTRP3 level, compared with non-obesity group, obesity group APN, CTRP3 level significantly decreased(P<0.05 or P<0.01).The leptin level elevated (P<0.05).2)APN concentration and age, BMI, FPG, TG, TC, LDL, FINs, HOMA-IR has negative correlation;CTRP3 andFPG,FINs, HOMA-negative correlation IR(P<0.05), TG was positively correlated (P<0.05);TNF-α and FPG and positively correlated (P< 0.05).Conclusions T2DM patients` serum APN, CTRP3 and high Leptin levels are closely associated with obesity, HOMA-IR, FPG and TG as an independent factor can be used as a new sensitive index of evaluating the degree of insulin resistance.
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OBJECTIVE@#To observe the clinical efficacy of sitagliptin plus insulin on patients with brittle diabetes and to determine the effect of the combined therapy on glucagon secretion. @*METHODS@#This randomized, double-blinded and placebo-controlled trial included 30 patients with brittle diabetes. Participants were randomly assigned (1:1) to receive the treatment of either sitagliptin plus insulin or placebo plus insulin for 12 weeks. The blood glucose, hemoglobin A1c, insulin dose, C-peptide, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and other parameters were determined. @*RESULTS@#After 12 weeks of treatment, blood glucose was controlled better by sitagliptin plus insulin (P<0.01). The patients had significantly lower glucose variability indices, lower daily insulin requirement and hemoglobin A1c in the group of sitagliptin plus insulin (P<0.01). After steamed bun test, past-meal GLP-1 levels at 30 min were higher (P<0.01) while GIP levels were lower (P<0.01), with glucagon suppression in the sitagliptin plus insulin group. No significant change was observed at any time point in placebo plus insulin group. @*CONCLUSION@#Sitagliptin significantly decreases blood glucose level and blood glucose fluctuation, which may contribute to the ability of sitagliptin in decreasing glucagon secretion.
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Humans , Blood Glucose , C-Peptide , Blood , Diabetes Mellitus, Type 1 , Drug Therapy , Dipeptidyl-Peptidase IV Inhibitors , Double-Blind Method , Drug Therapy, Combination , Gastric Inhibitory Polypeptide , Blood , Glucagon , Blood , Glucagon-Like Peptide 1 , Blood , Glycated Hemoglobin , Hypoglycemic Agents , Therapeutic Uses , Insulin , Therapeutic Uses , Sitagliptin Phosphate , Therapeutic UsesABSTRACT
The residents who had lived for at least 5 years and aged over 20 years old were sampled from urban to rural districts of Jiangsu Province with a stratified cluster sampling technique. B mode ultrasonography and thyroid function determination were carried out in 6 128 persons. The location, diameter, number, boundary, and calcification in thyroid nodules were described by using 7.5 MHz/50 mm transducer of thyroid ultrasonography. TSH was measured by chemiluminescence immunoassay. Free triiodothyronine(FT3)and free thyroxin(FT4)were measured when TSH was abnormal. The crude prevalence of thyroid nodules was 21.12% in total population, 14.55% in male, and 25.24% in female. The standardized prevalence was 15.69%, 11.20%, and 20.40%, respectively. The prevalence was lower in male than in female, and increased with age(P＜0.05). Thyroid nodules in Jiangsu Province were highly prevalent and more attention should be paid to the follow-up, early diagnosis, and treatment.
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A survey was conducted among 121 health care managers and health workers in community health care institutions with questionnaire and interview.Data on health care conditions in the community and health needs of elderly people were collected and analyzed using principle component analysis method.The priority order of 17 community health care projects for elderly people was ranked with this analysis method and the development strategy of community health service was suggested.
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Objective To explore the association of activated blood platelet and large vacular disease in type 2 diabetes mellitus.Methods A total of 98 cases of type 2 diabetes mellitus patients were divided into two groups(50 cases with large vascular disease and 48 cases,as DM group)and 50 cases healthy subjects served as a control group.From 2002-05 to 2004-11,the doctors of the Department of Endocrinology,Subei Hospital to determined the expression of platelet activation PAC-1、CD62P in large vascular disease by technique of flow cytometry(FCM),and glycosylated hemoglobin(HbA_1c)、C-reactive protein(CRP)、fasting plasama glucose(FBG)、C-peptide(C-P)and blood lipids were measured and analysed for the correlation.Results Activated blood platelet was significantly increased in DM group as compared with that in control group(P