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1.
Article in Chinese | WPRIM | ID: wpr-870155

ABSTRACT

Objective:To explore the clinical characteristics and follow-up outcomes of a pedigree of maturity onset diabetes of the young (MODY) induced by a novel mutation of glucokinase (GCK).Methods:The clinical features and laboratory data of a pedigree diagnosed with GCK-MODY in Peking Union Medical College Hospital was analyzed. Genomic DNA was extracted, and Sanger sequencing was performed to detect the gene mutation of the family members. The proband and her father were followed up for 3 years. Wanfang and PubMed were used to search literatures on follow-up studies for treatment of GCK-MOYD.Results:Both the proband and her father were found to have a novel mutation on the GCK gene located in exo10 c.1348G.T (p. Ala450Thr). The proband was treated with diet and exercise control only. At the end of the follow-up, her fasting plasma glucose (FPG, 6.8 mmol/L), 2 h postprandial plasma glucose (2hPG, 7.4 mmol/L), and glycated hemoglobin (HbA1c, 6.3%) were all within the control targets. Additionally, the levels homeostasis model assessment of insulin resistance (HOMA-IR) tended to improved comparing to that at baseline (4.09 to 2.32), and glucose disposition index (DI) was improved compared with baseline (16.22 to 20.05). As to the proband′s father, the treatment with insulin plus acarbose was converted to sulfonylureas monotherapy. His FPG and 2hPG mostly were within the target range, and the levels of HbA1c were significantly reduced by 0.5%-0.7% when compared to that at baseline. The HOMA-IR or islet beta cell function was comparable to those at baseline.Conclusions:Screening patients whose clinical performance meets GCK-MODY and their family members with proper genetic testing is of great importance to reduce misdiagnosis of GCK-MODY, so as to obtain a better glucose control without unnecessary over-treatment and protect islet beta cell function.

2.
Acta Pharmaceutica Sinica ; (12): 898-906, 2020.
Article in Chinese | WPRIM | ID: wpr-821681

ABSTRACT

Stroke has been harmful to human health for a long time, and there is no satisfactory treatment strategy because of its complex pathogenesis. Taohechengqi decoction has been effective in the treatment of stroke. In this study, the components were collected by TCMSP, TCMIP, BATMAN-TCM and TCMID databases, the targets were predicted and screened by PharmMapper and BATMAN-TCM databases, and the functional enrichment analysis of the targets was carried out by using R language package clusterProfiler. Finally, the key targets are verified by GEO database and molecular docking. The results showed that 51 active components of Taohechengqi decoction may regulate 15 key targets such as nitric oxide synthase, endothelial (NOS3), prostaglandin G/H synthase 2 (PTGS2), matrix metalloproteinase-9 (MMP9), affecting vascular endothelial growth factor signaling pathway and other pathways to play a role in the prevention of stroke, affecting tumor necrosis factor signaling pathway and other pathways to play a role in the treatment of stroke. GEO data analysis showed that androgen receptor (AR), caspase-8 (CASP8), intercellular adhesion molecule 1 (ICAM1), interleukin-1 beta (IL1B), mitogen-activated protein kinase 14 (MAPK14), MMP9, myeloperoxidase (MPO), peroxisome proliferator-activated receptor gamma (PPARG), PTGS2 and cellular tumor antigen p53 (TP53) were up-regulated genes, while serum albumin (ALB), estrogen receptor 1 (ESR1), NOS3, transcription factor p65 (RELA) and proto-oncogene tyrosine-protein kinase Src (SRC) were down-regulated genes. GEO analysis explained that Taohechengqi decoction may prevent stroke by down-regulating ESR1, NOS3, and treat stroke by up-regulating ICAM1, IL1B, MAPK14, MMP9, PPARG, PTGS2, TP53, and down-regulating RELA and SRC. The study found that in the process of prevention and treatment of stroke, Taohechengqi decoction played a two-way regulation role through multi-genes and multiple ways, which provided a new strategy for the treatment of stroke.

3.
Article in Chinese | WPRIM | ID: wpr-690289

ABSTRACT

Nonalcoholic fatty liver disease(NAFLD)refers to hepatic steatosis without other known causes such as alcohol abuse or hepatic virus infection. NAFLD has become a chronic disease worldwide,and its prevalence is constantly growing. Hepatic insulin resistance caused by obesity results in the deposition of triglycerides in the liver,promoting the occurrence and development of NAFLD. Weight loss is the only safe and effective method for NAFLD. Lifestyle intervention plays a cornerstone role in treating NAFLD;however,most patients can not achieve and maintain the ideal body weight by lifestyle intervention alone. Glucagon-like peptide-1 receptor agonist and metabolic surgery are promising treatments for NAFLD.

4.
Article in Chinese | WPRIM | ID: wpr-733936

ABSTRACT

Objective To compare glycemic profile between diabetic patients receiving peritoneal dialysis and diabetic patients with normal kidney function, and to investigate the impact of peritoneal dialysis on glycemic control through continuous glucose monitor system ( CGMS). Methods 19 diabetic patients with end-stage renal disease receiving regular peritoneal dialysis (DMPD group) and 8 patients with non-diabetic ne-phropathy receiving regular peritoneal dialysis ( PD group) were randomly selected and matched with 20 diabetic patients with normal kidney function (DM group) based on age, gender and 72 hours mean glucose. CGMS were applied on all patients for 72 hours. Glycemic variability parameters were compared among the three groups. Results Peritoneal transport function was positively correlated with mean glucose, glucose standard deviation and mean amplitude of glycemic excursion. Compared with PD group, multiple variation parameters, such as intraday glycemic standard deviation (P<0. 001), covariant efficiency (P=0. 009) and mean of daily difference (P=0. 043), were significantly lower in DMPD group. Though both DMPD and DM group exhibited profile as trough in wee hours and post-prandial hyperglycemia, DMPD had higher glycemic level in wee hours (P<0. 001). Conclusion Diabetic patients with end-stage renal disease receiving regular peritoneal dialysis have smaller glucose variability than diabetic patients with normal renal function.

5.
Journal of Medical Biomechanics ; (6): E325-E330, 2017.
Article in Chinese | WPRIM | ID: wpr-803883

ABSTRACT

Objective To study the effect of the icariin on apoptosis and cytoskeleton of osteoblasts in response to overload damage. Methods The four-point bending loading device was used to simulate the mechanical environment of overload damage and establish the cell overload damage model. According to whether the drugs were added before or after mechanical loading, the experiment was divided into blank control group, icariin group, damage group, damage prevention group and damage treatment group. Cell apoptosis was detected by flow cytometry. The specific fluorescent dyes were used to label the actin filament and the nucleus, and the changes of cytoskeleton were observed under laser scanning confocal microscope. Results Compared with control group, the apoptosis rate of damage group was the highest, and the icariin group was the lowest (P<0.05). Compared with damage group, the apoptosis rate of the damage prevention group was the lowest (P<0.05). The damage group showed cell shrinkage deformation, microfilaments disorganization, loosely arranged skeleton with vague outline, even broken skeleton. The morphological changes of cytoskeleton in damage prevention group were not significant, and there was no obvious change in cell nucleus. Conclusions Icariin can inhibit the apoptosis of osteoblasts after overload injury and maintain the stability of cytoskeleton to some extent.

6.
Article in Chinese | WPRIM | ID: wpr-615204

ABSTRACT

Objective To investigate clinical and pathological characteristics of insulin-induced localized lipoatrophy and treatment.Methods We retrospectively analyzed clinical manifestation, skin biopsy pathology, treatment regimen and follow-up of 6 diabetic patients with insulin-induced localized lipoatrophy in Peking Union Medical College Hospital from January, 2010 to March, 2016, with systemic review of related literatures.Results Among 6 cases with insulin-induced localized lipoatrophy, 5 patients were with insulin allergy.5 patients were with positive insulin-autoimmune antibody, which was similar to the ratio reported in the systematic review (18 out of 19).Insulin-induced lipoatrophy could be caused by various types of preparations of insulin and insulin analogs.Subcutaneous biopsy, performed on the atrophied area, revealed the decrease of the number and volume of adipocytes and tissue fibrosis, probably accompanied with lymphocytes, eosinophils or mast cells infiltration.Lipoatrophy could sometimes be relieved by changing injection sites, types of insulin preparations or drug-delivery way, sometimes by application of systemic/local glucocorticoid or local cromolyn sodium.Conclusions Insulin-induced localized lipoatrophy is a rare adverse reaction of insulin preparations.It might be related to immune response of local tissue and heterogeneous pathological manifestations.The lipoatrophy might be improved by changing injection sites, changing the type of insulin preparations or drug-delivery way, and with possibility to carry out targeted immunosuppressive therapy according to the biopsy pathology in the future.

7.
Basic & Clinical Medicine ; (12): 682-686, 2017.
Article in Chinese | WPRIM | ID: wpr-512264

ABSTRACT

Objective To explore the relationship between SNPs in microRNA binding sites of ABCG5/8 and the glucolipid level during pregnancy.Methods 1 925 pregnant women were recruited at Peking Union Medical College hospital from 2006 to 2011.The clinical data were collected and the total genomic DNA was extracted from whole blood samples.ABCG5/8, which was reported to be related with the glucose and lipid metabolism closely, were selected as the candidate gene and the SNPs in its microRNA binding sites with minor allele frequency >5% in Han Chinese in Beijing were chosen.Then the genotyping was performed and analyzed.Results There was only one SNP matching the criteria, rs2278356, and it is significantly associated with LDL-C and TC level during pregnancy (LDL-C: b=0.104 mmol/L, 95% CI 0.023-0.185 mmol/L, P<0.05;TC: b=0.105 mmol/L, 95% CI 0.080-0.203 mmol/L, P<0.05).Conclusions The association of rs2278356 in 3′UTR of ABCG5/8 with LDL-C and TC level in pregnant Chinese Han women is found, which may provide an individualized treatment strategy for pregnant women with high cholesterol.

8.
Article in English | WPRIM | ID: wpr-311364

ABSTRACT

The study illustrate the inner correlation between global DNA methylation variation and different birth weights. Infant birth weight was used to identify cases and controls. Cord blood and placentas were collected. We performed DNA methylation profiling of bisulphite-converted DNA. We have identified many differentially methylated CpG sites in experimental groups; these sites involved in hundreds of signalings. Among these, more than ten pathways were referred to the glucose and lipid metabolism. Methylation changes in the insulin-signaling pathway (ISP), adipocytokine signaling pathway (ASP) and MAPK signaling pathway are involved in the fetal programming of diabetes..


Subject(s)
Birth Weight , DNA Methylation , Female , Gene Expression Regulation, Developmental , Physiology , Genome-Wide Association Study , Humans , Infant, Newborn , Male , Organ Size , Placenta , Pregnancy , Signal Transduction
9.
Article in Chinese | WPRIM | ID: wpr-496742

ABSTRACT

Objective To investigate the effects of initiating oral-medication and insulin-treatment to residual islet function in adult patients with latent autoimmune diabetes in adults (LADA).Methods Fifty nice inpatients and 11 outpatients of LADA were enrolled from the Peking Union Medical College Hospital from January 1981 to October 2014,including 34 cases with initiating insulin therapy and 36 cases with initiating oral medication.Patients were followed up at least twice and with a 6-month interval.The age,body mass index (BMI),diagnosis time,fasting C peptide (FCP),2-hour postprandial C peptide (2 hCP),glycosylated hemoglobin (HbA1c) were compared between two groups.Results The age of disease onset in insulin-treatment group was significantly lower than that in oral-medication group (t =2.049,P =0.045).The proportion of patients complicated with other autoimmune diseases in oralmedication group were higher than that in insulin-treatment group [24% (8/34) vs.47% (17/36),x2=4.275,P=0.039].The FCP and 2 hCP in insulin-treatment group were significantly higher than those in oral-medication group [FCP:0.25 (0.00-0.80) vs.0.00 (0.00-0.60) μg/L,Z =3.498,P =0.030,2 hCP:0.42(0.02-1.20) vs.0.14(0.02-0.19) μg/L,Z =3.235,P=0.001] on 6 month after treatment;however,there were no significant differences on 6-12 months,13-36 months or 37-60 months after treatment between two groups.No antibody negative conversion was detected in 10 inpatients,who were reexamined with glutamic acid decarboxylase antibody (GADA) more than twice.The detection rate of diabetes retinopathy was 4% (1/26) in insulin-treatment group and 28% (8/29) in oralmedication group (x2 =6.179,P =0.013).Conclusion Initiating insulin therapy at first diagnosis of LADA can protect the residual islet function,and may reduce the rate of diabetic retinopathy.

10.
Article in English | WPRIM | ID: wpr-289869

ABSTRACT

Objective To explore the associations of white blood cell (WBC) count,alanine aminotransferase (ALT),and aspartate aminotransferase(AST) in the first trimester of pregnancy with gestational diabetes mellitus (GDM). Methods Totally 725 GDM women and 935 women who remained euglycemic throughout pregnancy were enrolled in this study. Pre-pregnancy weight/height were recorded. WBC,ALT,and AST levels were detected between 8 and 12 weeks of pregnancy.At 24 to 28 weeks of pregnancy,the glucose and insulin levels were measured. The WBC,ALT,and AST levels were compared between two groups,and the associations of WBC,ALT,and AST levels with the blood glucose and insulin levels were retrospectively analyzed. Meanwhile,the potential associations of those factors with the occurrence of GDM were analzyed. Results WBC count [9.41(8.15,10.84)?10(9)/L vs. 9.04 (7.64,10.37)?10(9)/L,P=1.0?10(-5)] and ALT levels [18.00(12.00,30.00)U/L vs. 16.00 (11.00,26.00)U/L,P=0.004] in the first trimester of pregnancy were significantly increased in GDM subjects than in normal glucose tolerance(NGT)subjects;however,the AST level showed no significant difference between these two groups [41.00 (26.00,43.00)U/L vs. 41.00 (23.00,43.00)U/L,P=0.588]. Logistic regression analysis illustrated that elevated WBC count was an independent risk factor for GDM after adjustment for age,pre-pregnancy body mass index,blood pressure,and family history of diabetes(OR=1.119,P=0.001). The ROC curve revealed that threshold of WBC count was 7.965?10(9)/L(AUC=0.566,P=1?10(-5)),which had a sensitivity of 79.4% and a specificity of 31.3%. Multivariate linear regression analysis showed that homeostasis model assessment of insulin resistance was positively correlated with WBC count(B=0.051,P=0.022,R(2)=0.083);1-hour blood glucose after oral 50 grams of sugar (B=0.044,P=0.001,R(2)=0.044) and fasting plasma true insulin(B=0.214,P=0.032,R(2)=0.066) were positively correlated with WBC count;1-hour true insulin after 100 grams oral glucose to lerance test(OGTT) was positively correlated with AST (B=0.616,P=1.85?10(-5),R(2)=0.052);2-hour true insulin after 100 grams OGTT was positively correlated with ALT (B=0.148,P=0.027)and AST(B=0.936,P=3.71?10(-8),R(2)=0.077);and 3-hour true insulin after 100 grams oral glucose tolerance test(OGTT) was positively correlated with ALT (B=0.189,P=0.002) and AST (B=0.688,P=7.25?10(-6),R(2)=0.067).Conclusions The WBC count in the first trimester of pregnancy can increase the risk of GDM. Thus,WBC count may be a useful predictors of GDM.


Subject(s)
Alanine Transaminase , Blood , Aspartate Aminotransferases , Blood , Blood Glucose , Case-Control Studies , Diabetes, Gestational , Blood , Female , Glucose Tolerance Test , Humans , Insulin , Blood , Insulin Resistance , Leukocyte Count , Pregnancy , Pregnancy Trimester, First , Risk Factors
11.
Article in English | WPRIM | ID: wpr-281447

ABSTRACT

Objective To retrospectively analyze the clinical characteristics of 261 cases of hospitalized patients with type 1 diabetes mellitus (T1DM) in Peking Union Medical College Hospital (PUMCH).Methods Clinical data of 261 cases of hospitalized patients diagnosed with T1DM in the Department of Endocrinology at PUMCH from January 2007 to December 2014 were analyzed retrospectively. All patients were divided into the T1DM antibodies positive group (n=180) and negative group (n=81) according to the results of immunohistochemistry, in which 123 newly diagnosed T1DM patients were divided into the adult onset group (>18 years, n=58) and non-adult onset group (≤18 years, n=65) according to the onset age of T1DM, respectively. The clinical characteristics from different groups were compared.Results In 261 patients, the average age was 26.6±15.4 years, the average disease duration was 49 (1-480) months, the positive rate of antibodies to glutamic acid decarboxylase antibody was 58.8% (153/260). The level of 2-hour postprandial C peptide and the positive rate of T1DM antibodies in the non-adult onset group were higher than those in the adult onset group (0.98 vs. 0.52 ng/ml, P=0.002 and 80.4% vs. 62.5%, P=0.048). The age of onset in the T1DM antibodies positive group was smaller than that in the T1DM antibodies negative group (19.7±11.4 vs. 24.7±15.6 years, P=0.04), while the incidence of ketosis in the T1DM antibodies positive group was higher than that in the T1DM antibodies negative group (48.3% vs. 34.2%, P=0.035). With the progress of the disease, the fasting C peptide level of the T1DM antibodies positive group decreased more rapidly. Compared with the single time hospitalized patients, multiple hospitalized patients had a lower incidence of diabetic retinopathy (8.2% vs. 22.4%, P=0.032), a lower hemoglobin A1level (8.04%±2.10% vs. 9.56%±2.64%, P<0.001) and fasting blood glucose level (8.7±3.1 vs. 10.9±4.2 mmol/L, P<0.001).Conclusions Compared with the non-adult onset T1DM patients, the islet function of adult onset patients was even worse. In the T1DM antibodies positive patients, the islet β cell function decreased more rapidly, so the antibodies could not only clarify the diagnosis of T1DM and also predict prognosis of the islet β cell function. In the management of T1DM patients, regular hospital revisits contributed to get better glycemic control and reduced the occurrence of diabetic complications.

12.
Journal of Experimental Hematology ; (6): 1725-1729, 2016.
Article in Chinese | WPRIM | ID: wpr-332621

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of arsenic trioxide (AsO) on K562 cell proliferation by regulating cell cycle protein D1 and cyclin-dependent kinase inhibitor p27kip1.</p><p><b>METHODS</b>MTT was used to detect the effect of AsOon K562 cell proliferation, so as to screen out the appropriate drug concentration. Furthermore, the K562 cell apoptosis was observed by microscopy. The expression of CyclinD1 and p27kip1 in K562 cells treated with AsOwas analyzed by reverse transcription-polymerase chain reaction(RT-PCR), immunohistochemistry and Western blot.</p><p><b>RESULTS</b>AsOcould inhibit the proliferation of K562 cells in a dose- and time- dependent manner (r= 0.967). And the apoptosis cell number in AsOgroup was significantly higher than that in the control group(P<0.05). AsOcould markedly inhibit the expression of CyclinD1 in K562 cells(P<0.05), but the expression of P27kip1 was not significantly changed after AsOtreatment.</p><p><b>CONCLUSIONS</b>AsOcan induce K562 cell apoptosis and inhibit K562 cell proliferation by regulating the expression of CyclinD1.</p>

13.
Journal of Medical Postgraduates ; (12): 763-766, 2015.
Article in Chinese | WPRIM | ID: wpr-461760

ABSTRACT

Urid acid is one of the terminal metabolites of human body.More and more attention was paid to its metabolic mechanisms in intestinal tract;however, few studies were seen so far.This study aims to illuminate the metabolic mechanism of uric acid in intestinal tract by two ways:one is the transporters associated with intestinal epithelium, including ABCG2 and SLC2A9, the other is decomposition of uric acid by intestinal flora.We hope this review can provide new insights to decrease blood uric acid and treat urate-related diseases, and also provide a new way to alleviate drug-induced kidney damage.

14.
Article in Chinese | WPRIM | ID: wpr-357324

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of mannan-binding lectin (MBL) on the maturation and cytokine secretion of human dendritic cells (DC) induced by Candida albicans (C. albicans).</p><p><b>METHODS</b>The plastic-adherent mononuclear cells were prepared from the blood of healthy adult volunteers. The human peripheral blood mononuclear cells-derived dendritic cells (MNC-DC) were induced by 5-day-culture in medium supplemented with rhGM-CSF and rhIL-4, and then cultured for 2 days in presence or absence of C. albicans at varying concentration of human MBL ranging from 1 to 20 mg/L. DC's shape and characters were observed under inverted microscopy, the expression of CD83 and CD86 on DC was analyzed by FACS. The levels of TNF-α and IL-6 were detected by ELISA. FACS also was used to investigate the interaction of MBL with immature DC(imDC) and C. albicans. Western blot was used to detect C. albicans-induced IκBα phosphorylation and p65/NF-κB translocation in DC.</p><p><b>RESULTS</b>MBL at higher concentrations (10-20 mg/L) down-regulated the expression of CD83 and CD86 on the monocyte-derived dentritic cells(MoDC) induced by C. albicans, and inhibited the production of TNF-α and IL-6 induced by C. albicans. FACS showed that MBL could not only bind to C. albicans but also bind to imDCs in a Ca2+-dependent manner. Western blot showed that MBL could decrease the phosphorylation of IκBα and the nuclear translocation of p65/ NF-κB.</p><p><b>CONCLUSION</b>MBL may inhibit TNF-α and IL-6 production induced by C. albicans in DC through NF-κB signaling pathways, suggesting that MBL can play some roles in the regulation of C. albicans-induced immune response.</p>


Subject(s)
Candida albicans , Cell Differentiation , Cytokines , Dendritic Cells , Humans , Mannose-Binding Lectin , NF-kappa B , Protein Transport
15.
Journal of Integrative Medicine ; (12): 162-70, 2014.
Article in English | WPRIM | ID: wpr-450232

ABSTRACT

Chromium is an essential mineral that is thought to be necessary for normal glucose homeostasis. Numerous studies give evidence that chromium picolinate can modulate blood glucose and insulin resistance. The main ingredient of Tianmai Xiaoke (TMXK) Tablet is chromium picolinate. In China, TMXK Tablet is used to treat type 2 diabetes. This study investigated the effect of TMXK on glucose metabolism in diabetic rats to explore possible underlying molecular mechanisms for its action.

16.
Journal of Integrative Medicine ; (12): 162-170, 2014.
Article in English | WPRIM | ID: wpr-308206

ABSTRACT

<p><b>OBJECTIVE</b>Chromium is an essential mineral that is thought to be necessary for normal glucose homeostasis. Numerous studies give evidence that chromium picolinate can modulate blood glucose and insulin resistance. The main ingredient of Tianmai Xiaoke (TMXK) Tablet is chromium picolinate. In China, TMXK Tablet is used to treat type 2 diabetes. This study investigated the effect of TMXK on glucose metabolism in diabetic rats to explore possible underlying molecular mechanisms for its action.</p><p><b>METHODS</b>Diabetes was induced in rats by feeding a high-fat diet and subcutaneously injection with a single dose of streptozotocin (50 mg/kg, tail vein). One week after streptozotocin-injection, model rats were divided into diabetic group, low dose of TMXK group and high dose of TMXK group. Eight normal rats were used as normal control. After 8 weeks of treatment, skeletal muscle was obtained and was analyzed using Roche NimbleGen mRNA array and quantitative polymerase chain reaction (qPCR). Fasting blood glucose, oral glucose tolerance test and homeostasis model assessment of insulin resistance (HOMA-IR) index were also measured.</p><p><b>RESULTS</b>The authors found that the administration of TMXK Tablet can reduce the fasting blood glucose and fasting insulin level and HOMA-IR index. The authors also found that 2 223 genes from skeletal muscle of the high-dose TMXK group had significant changes in expression (1 752 increased, 471 decreased). Based on Kyoto encyclopedia of genes and genomes pathway analysis, the most three significant pathways were "insulin signaling pathway", "glycolysis/gluconeogenesis" and "citrate cycle (TCA)". qPCR showed that relative levels of forkhead box O3 (FoxO3), phosphoenolpyruvate carboxykinase 2 (Pck2), and protein tyrosine phosphatase 1B (Ptp1b) were significantly decreased in the high-dose TMXK group, while v-akt murine thymoma viral oncogene homolog 1 (Akt1) and insulin receptor substrate 2 (Irs2) were increased.</p><p><b>CONCLUSION</b>Our data show that TMXK Tablet reduces fasting glucose level and improves insulin resistance in diabetic rats. The mechanism may be linked to the inactivation of PTP1B and PCK enzymes, or through intracellular pathways, such as the insulin signaling pathway.</p>


Subject(s)
Animals , Blood Glucose , Chromium , Diabetes Mellitus, Type 2 , Drug Therapy , Metabolism , Insulin , Physiology , Insulin Resistance , Male , Medicine, Chinese Traditional , Phosphoenolpyruvate Carboxykinase (ATP) , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Signal Transduction , Tablets
17.
Article in Chinese | WPRIM | ID: wpr-332696

ABSTRACT

The study was aimed to investigate the mechanism of mannan-binding lectin (MBL) on bacterial lipopolysaccharide (LPS)-induced human peripheral blood monocyte-derived dendritic cell (DC) maturation. The monocytes were prepared from the peripheral blood of healthy adult volunteers. The immature dendritic cells (imDC) were induced by 5-day-culture in medium supplemented with rhGM-CSF and rhIL-4. FACS was used to investigate the interaction of MBL with imDC and the impact of MBL on LPS binding to imDC. ELISA and Western blot was used to analyze the interaction of MBL with soluble TLR4 ectodomain protein (sTLR4); Western blot was used to detect LPS-induced NF-κB translocation in imDC. The results showed that MBL could directly bind to imDC in the presence of calcium. sTLR4 protein or LPS could competitively inhibit the binding of MBL to imDC. ELISA and Western blot showed that MBL could evidently bind to sTLR4 protein in a concentration-dependent manner. FACS showed that MBL could competitively inhibit the binding of LPS to imDC by binding to imDC directly. Western blot showed that MBL decreased LPS-induced NF-κB translocation in imDC. It is concluded that MBL may competitively inhibit the binding of LPS to imDC by binding to TLR4 expressed on imDC, resulted in inhibition of LPS-induced DC maturation, suggesting that MBL can regulate DC maturation through ligand-binding. This study provides the good foundation to clarify the mechanism of MBL inhibiting the LPS-induced DC maturation.


Subject(s)
Cell Differentiation , Cells, Cultured , Dendritic Cells , Cell Biology , Metabolism , Humans , Ligands , Lipopolysaccharides , Mannose-Binding Lectin , Pharmacology , Monocytes , Cell Biology , Metabolism , Toll-Like Receptor 4 , Metabolism
18.
Article in English | WPRIM | ID: wpr-358708

ABSTRACT

High-altitude hypoxia can induce physiological dysfunction and mountain sickness, but the underlying mechanism is not fully understood. Corticotrophin-releasing factor (CRF) and CRF type-i receptors (CRFR1) are members of the CRF family and the essential controllers of the physiological activity of the hypothalamo-pituitary-adrenal (HPA) axis and modulators of endocrine and behavioral activity in response to various stressors. We have previously found that high-altitude hypoxia induces disorders of the brain-endocrine-immune network through activation of CRF and CRFR1 in the brain and periphery that include activation of the HPA axis in a time- and dose-dependent manner, impaired or improved learning and memory, and anxiety-like behavioral change. Meanwhile, hypoxia induces dysfunctions of the hypothalamo-pituitary-endocrine and immune systems, including suppression of growth and development, as well as inhibition of reproductive, metabolic and immune functions. In contrast, the small mammals that live on the Qinghai-Tibet Plateau alpine meadow display low responsiveness to extreme high-altitude-hypoxia challenge, suggesting well-acclimatized genes and a physiological strategy that developed during evolution through interactions between the genes and environment. All the findings provide evidence for understanding the neuroendocrine mechanisms of hypoxia-induced physiological dysfunction. This review extends these findings.


Subject(s)
Altitude , Animals , Brain , Corticotropin-Releasing Hormone , Metabolism , Hypothalamo-Hypophyseal System , Hypoxia , Pituitary-Adrenal System , Receptors, Corticotropin-Releasing Hormone , Metabolism , Tibet
19.
Article in English | WPRIM | ID: wpr-235524

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the association between vitamin D deficiency and risk of gestational diabetes mellitus (GDM) in pregnant Chinese women.</p><p><b>METHODS</b>A nested case-control study was conducted. Clinical and biochemical data were analyzed for 200 subjects with GDM and 200 subjects with normal glucose tolerance (NGT).</p><p><b>RESULTS</b>The median (interquartile range) serum 25-hydroxyvitamin D (25OHD) levels were 22.39 (17.67, 29.38) and 25.86 (19.09, 34.88) nmol/L in the GDM and NGT groups, respectively. Rates of 25OHD deficiency or insufficiency were significantly higher in the GDM group than in the NGT group. Subjects with 25OHD levels <25 nmol/L had a 1.8-fold higher risk of GDM compared with subjects with higher vitamin D levels. In the GDM group, serum 25OHD was independently associated with HbA1c and insulin resistance after adjusting for confounding factors. In the NGT group, serum 25OHD was independently associated with fasting plasma glucose and systolic blood pressure after adjusting for maternal age and other confounding factors.</p><p><b>CONCLUSION</b>25OHD insufficiency is very common in Chinese women. Low 25OHD status may be associated with insulin resistance and act as a risk factor for GDM.</p>


Subject(s)
Adult , Asian Continental Ancestry Group , Diabetes, Gestational , Blood , Epidemiology , Female , Humans , Pregnancy , Vitamin D , Blood , Vitamin D Deficiency , Blood , Epidemiology
20.
Article in Chinese | WPRIM | ID: wpr-384488

ABSTRACT

Objective To investigate the relationship between gene polymorphism of transcripion factor 7-like 2 (TCF7L2) at positions rs290487, rs11196205, rs11196218 and gestational diabetes mellitus (GDM) in Chinese women.Methods In 1140 unrelated pregnant Northern Chinese women (335 women with GDM, 158 gestational cases with impaired glucose tolerance and 647 pregnant non-diabetic controls) ,three single nucleotide polymorphisms (rs290487, rs11196205, and rs11196218) in the TCF7L2 gene were genotyped using ligase detection reaction (LDR).In the present study, cases with GDM and impaired glucose tolerance (IGT) were indistinguishable clinically and biochemically, and were combined into case group.Results The frequency of C allele of rs290487 was 41.6% in case group, being significantly higher than that in control group (36.3%, P=0.012).There was significant difference in the frequency of CC genotype between case group and control group (18.7% vs 14.0%, P=0.033).Compared with T allele carriers, CC genotype carriers had a 1.418-fold increased risk of GDM (95% CI 1.028-1.955).After adjusting for age, body mass index, family history of diabetes,systolic blood pressure,and diastolic blood pressure, pregnant women with CC genotype carriers of rs290487 were more prone to hyperglycemia compared with the T allele carriers (OR 1.518, 95% CI 1.064-2.166).Conclusions The TCF7L2 rs290487 variant may contribute to the genetic predisposition to GDM.CC genotype is likely to be associated with an increased risk of GDM in the pregnant Chinese women.

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