ICOSL could upregulate immune response in Graves′s disease animal models / 中国免疫学杂志

Objective:To study the pathological mechanism of the inducible co-stimulator molecular and ligand ( ICOS/ICOSL) in Graves disease animal.Methods:45 out-bred BALB/c mice were randomly divided into three groups with 15 rats in each group;using gene gun to deliver different plasmid injection.Group A was delivered with pCDNA3.0-mICOSL and pCDNA3.0-hTSHR, Group B with pCDNA3.0-hTSHR and null pCDNA3.0 with Group C for immunization as the control group.The concentration of serum free thyroxine immunization was deter mined with immunoassay and serum thyrotropin receptor antibody ( TRAb ) with ELISA, supernatant of IFN-γconcentration in mouse spleen cells was measured with radioimmunoassay,and hTSHR transected CHO cells were incubated to detect the concentration of cAMP to deter mine autoantibody TRAb activity.Results: After plasmid injection serum FT4 level in Group A (0.49±0.25) pg/ml ( q=6.571,P=0.023) was higher than that in Group C,the standard rate was higher than Group B and C (χ2=14.47,P=0.005).IFN-γconcentration of mice spleen cultured supernatant in Group A (1.88±0.41) pmol/L was significantly higher than the other two groups.The activity of autoantibody TRAb in Group A 188.3 (179.7-260.2) %was higher than that in the other two groups ( P=0.027 ) .Conclusion: Exogenous delivery of pCDNA3.0-mICOSL plasmid in GD mice could stimulate the spleen lymphocytes to secrete more IFN-γ,increase the activity of TRAb autoantibodies and might lead to upregulation of immune response in Graves animal model in vivo.

Effect of 11β-hydroxysteroid dehydrogenase type 1 gene silencing on glucose stimulated insulin secretion of pancreatic β cell line NIT-1 / 基础医学与临床

Objective To investigate the effect of small interference RNA (siRNA) targeting at 11β-hydroxysteroid dehydrogenase type 1 on the glucose-stimulated insulin secretion (GSIS) in pancreatic β cell line NIT-1 cell.Methods siRNA plasmid vectors specifically targeting at 11β-HSD1 gene were constructed,named as olig886,oligo866 and scrabble control for oligo886,then tansfected into NIT-1 cells.The expression of 11β-HSD1 was detected by RT-PCR and Western blot.O1igo886 vector was transfected into the NIT-1 cells in 25 mmol/L glucose concentrations medium.The insulin secretion level was measured in GSIS test.Results After treatment with 11β-HSD1 siRNA,the mRNA level of 11β-HSD1 in NIT-1 cell was decreased by 78.1%±2.9% and 51.7% ±2.7% inolig886 and oligo866 group respectively.The protein of 11β-HSD1 were decreased by 82.2% ±2.1% and 56.5%±2.0 % respectively.After transfected by olig 8 8 6 vector,the insulin secretion increased in NIT -1 cell.Conclusion 11β-HSD1 gene silencing may improve GSIS in NIT-1 cell 11β-HSD1 regulate local glucocorticoid metabolism in pan-creatic islet and affect the function of insulin secretion.

rAAV-mediated VLDLR gene transfection reduces tau hyperphosphorylation in hippocampus of type 2 diabetic rats / 中国病理生理杂志

AIM: Abnormal hyperphosphorylation of tau plays a critical role in the pathogenesis of Alzheimer's disease(AD), and tau protein was hyperphosphorylated in type 2 diabetes. The present study was designed to explore the phosphorylation level of tau in hippocampus of type 2 diabetes rats which interrupted by very low density lipoprotein receptor(VLDLR)gene transfection. METHODS: Wistar male rats were randomized into 3 groups. The control group(CTL)was fed with normal food. The T2DM group and T2DM mediated VLDLR gene group were on high sugar, high fat and high protein diet for 3 months. The plasma insulin level was measured by RIA method, and the plasma glucose was determined by glucose-oxidase method. Total tau level, the phosphorylation level of tau at individual phosphorylation sites and the level of VLDLR were analyzed by Western blotting. The activity of glycogen synthase kinase 3β, a key component of insulin signal transduction pathway and a known tau kinase, in the hippocampus of rats was determined by using [γ-~(32)P]-ATP and the specific peptide substrate. RESULTS: No significant difference of total tau level in hippocampus between T2DM group and T2DM mediated VLDLR gene group was observed. Tau protein in T2DM group was found to be more hyperphosphorylated at several AD-related phosphorylation sites(Ser214, Thr217, Ser396, Ser422 and Ser199/202)than that in CTL, while the immunoreaction at tau-1 site is weaker than that in CTL. VLDLR gene therapy reduced hyperphosphorylation sites of Thr217, Ser396, Ser422 and Ser199/202 of tau to almost the control level, but did not change the phosphorylation of Ser214 or Ser422 on tau. The expression of Ser214 was also observed by immunohistochemical assay. The phosphorylated tau modestly increased in hippocampus in T2DM group compared to CTL, but VLDLR gene treatment did not change the phosphorylation level. The phosphorylation of GSK-3β was decreased dramatically in the hippocampus in T2DM rats, and this phosphorylation was significantly increased after VLDLR gene treatment. CONCLUSION: These findings suggest that Raav mediated VLDLR gene treatment partially reverses tau hyperphosphorylation at several sites in T2DM rat hippocampus, which may mediate by inhibition of GSK-3β activity.

Influence of Wnt signaling pathway on mouse NIT-1 β-cell cultured in vitro / 中华内分泌代谢杂志

Objective To establish whether Wnt-signaling pathway plays a role in mice β-cell function and/or survival in vitro. Methods Mice NIT-1 beta cells were cultured in media with glucose concentration of 33.3 mmol/L and the cytokines interleukin-1β, interferon-γand tumor necrosis factor-α with or without the addition of purified Wnt3a protein in vitro. Subsequently, β-cell apoptosis by Tunnel and flow cytometry, and β-cell proliferation by BrdU were analyzed. Total RNA was extracted to measure gene expressions by real-time PCR.Results Incubations of NIT-1 cells with high glucose and cytokines resulted in an increase in β-cell apoptosis and decrease in β-cell proliferation (P<0.01). In contrast, treatment with Wnt3a protein protected β-cell from glucose and cytokines-induced apoptosis through up-regulating the expressions of above Pitx2、 TCF7L2. Conclusions Wnt-signaling regulates the proliferation of pancreatic β-cell, and protectes β-cell from glucotoxicity and cytokine toxicity with respect to proliferation and apoptosis.

Study on 746 cases of pituitary adenomas treated with surgery / 中华内分泌代谢杂志

Objective To analyze the clinical data, including clinical features, treatment, and prognosis,in patients with different kinds of pituitary adenomas. Methods In this retrospective study, 746 cases were included. The characteristics of general epidemiology, clinical symptoms, pathology, imaging, treatment, and prognosis were analyzed. Results Clinical features were different among various pituitary adenomas. Symptoms caused by mass effect and hormone abnormality were expresssed in varying degrees. Serum prolactin>121.28 μg/L can differentiate the prolactin adenoma from the other huge tumor causing hyperprolactinemia due to the mass effect. There is significant relationship between the size and the various types of pituitary adenomas ( P<0.01 ),also between the size and the invasive capability ( P<0.01 ). Conclusions The pituitary adenomas may have their specific epidemiological, clinical, pathological, and imaging features, due to the distinct biological behavior. It is necessary to do the diagnosis, treatment, and prognosis evaluation individually.

Biphasic insulin aspart 30 plus metformin in patients with type 2 diabetes inadequately controlled on basal insulin therapy:An evaluation of efficacy and safety / 中华内分泌代谢杂志

Objective To evaluate the efficacy and safety of biphasic insulin aspart 30 (BIAsp30)plus metformin in type 2 diabetes subjects switching from basal insulin plus oral antidiabetic drugs (OAD)Methods During 16 weeks, multiple-center, open-label, and single-arm study including 2 weeks of screening period,4 weeks of run-in period,and 16 weeks of treatment period were carried out. Subjects with type 2 diabetes mellitus inadequately controlled on basal insulin therapy with or without oral antidiabetic drugs were switched to twice-daily BIAsp30 plus metformin with dose titration to achieve fasting plasma glucose target. Results Of the 293 Chinese subjects exposed to trial drugs [age: ( 54.0±9.6 ) years, diabetes duration: ( 8.54±5.49 ) years, body mass index: (24.89±3.28)kg/m2, baseline HbA1c: 8.16% ±0.89%], 122 were previously treated with basal insulin analogues and 169 with human basal insulin. At end of the trial ,the mean reduction of HbA1 c was 1.30% ±0.96% (P＜0. 01 ). The proportion of patients achieved HbA1c＜7.0% and HbA1c ≤6.5% was 60.4% and 38.9% respectively. 8-point plasma glucose measurements showed significant improvements at all the time points examined ( all P＜0. 01 ) ,and the average value of all 8 points measured decreased from ( 10.53±2.58 ) mmol/L atbaseline to (7.79± 1.58 ) mmol/L at the end of treatment ( P＜0. 01 ), reduced by 2.76 mmol/L. Postprandial glucose increments were significantly reduced after breakfast ( -1.73 mmol/L,P＜0.01 )and dinner ( -1.28 mmol/L,P＜0.01 ), while no significant reduction was observed after lunch ( -0.09 mmol/L, P = 0. 734 5 ). No severe adverse effect and no major hypoglycemia were reported. The overall hypoglycaemia rate was 2.68 events/subject year. The average weight gain was (0. 76 ±0. 14 )kg (P＜0. 0l ). Conclusion Twice-daily BIAsp30 plus metformin is effective and safe to type 2 diabetic subjects inadequately controlled on basal insulin treatment.BIAsp30 treatment should be considered for type 2 diabetic subjects who have unsatisfactory response to previous basal insulin treatment.

Effects of high concentration glucose on the expression of NF-kappaB, Bax and cytochrome C and apoptosis of islet cells in mice / 华中科技大学学报（医学）（英德文版）

The roles of NF-kappaB (NF-kappaB) expression, Bax activity and cytochrome C (Cyt C) release, apoptosis of islet cells induced by high concentration glucose were explored in vitro. Pancreatic islet cells, which were isolated from Kunming mice, were cultured with different concentrations of glucose in DMEM, and divided into the following groups: G1, G2, G3, G4, G5, and G6 groups, corresponding to the glucose concentrations of 5.6, 7.8, 11.1, 16.7, 22.5, and 27.6 mmol/L, respectively. After culture for 120 h, insulin secretion was evaluated by radioimmunoassay, and the NF-kappaB expression was detected by immunocytochemistry. Bax activity and Cyt C release were measured by immunofluorescence, and apoptosis was examined by Hoechst33342 assay. The results showed that in G1, G2 and G3 groups, insulin secretion was enhanced with the increase of glucose concentration, and the NF-kappaB expression was also increased (P<0.05), but Bax activity, Cyt C release and apoptosis rate showed no significant difference among them. However, in G4, G5, and G6 groups, apoptosis rate of islet cells, NF-kappaB expression, Bax activity, and Cyt C release were all significantly increased, and insulin secretion was impaired as compared with G1, G2, and G3 groups (P<0.05). It was concluded that the exposure of islet cells to high glucose could induce islet cells apoptosis as well as impaired insulin secretion. The NF-kappaB signaling pathway and mitochondria pathway in islet cells might play some roles in the progressive loss of islet cells in diabetes. The inhibition of the NF-kappaB expression could be an effective strategy for protecting pancreatic islet cells.

Relationship of plasma acylation stimulating protein with blood lipid profile in women with pulycystic ovary syndrome / 中华内分泌代谢杂志

Objective To study the relationship of plasma aeylation stimulating protein (ASP) with complement C3, C-reactive protein (CRP) and blood lipid levels in women with polyeystic ovary syndrome (PCOS). Methods Thirty-four patients with PCOS were divided into two groups: obese PCOS group [body mass index (BMI)≥25 kg/m2] and non-obese PCOS group (BMI<25 kg/m2). 41 age-matched non-PCOS women were also divided into two groups: simply obese group (BMI≥25 kg/m2) and non-obese control group (BMI <25kg/m2). Plasma ASP in the 4 groups was detected by enzyme linked immunosorbent assay (ELISA) method.Complement C3 and CRP were determined by immunoturbidimetrie assay. Plasma free fatty acid (FFA)concentration was determined by colorimetric enzymatic assay, plasma triglycerides (TG) by GPO-PAP method and total cholesterol (TC) by COD-PAP method. Results The plasma ASP were significantly increased in the obese PCOS group, the non-obese PCOS group and the obese group as compared with the control group [(36.4±10.9,34.8±9.9, 35.1±14.0, 24.8±7.8) nmol/L, respectively, all P<0.05]. The concentrations of complement C3 were significantly higher in the obese PCOS group and the obese group than that in the control group [(2.2±1.2,2.5±1.5, 1.1±0.7) g/L, respectively, bothP <0.05]. The concentrations of CRP were significantly increased in the obese PCOS group, non-obese PCOS group and obese group as compared with the control group [(32.1±29.2, 30.0±24.8, 23.8±5.5, 7.5±4.8)mg/L, respectively, all P<0.05]. Univariate analysis showed that both plasma ASP and C3 were positively correlated with BMI, CRP, FFA and TG. CRP was positively correlated with BMI, FFA, TG and TC. Conclusion Plasma ASP, C3 and CRP levels in women with PCOS axe increased. They are strongly associated with disturbed lipid metabolism. The lack of association between ASP and complement C3 suggests that the conversion of C3 to ASP may be affected by other factors.

Expression of c-met stimulated by high glucose in human renal tubular epithelial cells and its implication / 华中科技大学学报（医学）（英德文版）

The expression of c-met stimulated by high glucose in human renal tubular epithelial cells and the role of HGF/c-met system in diabetic nephropathy were examined. The proximal tubular epithelial cells were cultured in vitro under different conditions. MTT was used for the detection of cellular proliferation and RT-PCR was employed for measurement of c-met mRNA level. Our results showed that under different conditions, there were no significant differences in the proliferation of proximal tubular epithelial cells 12 h and 24 h after the culuture (P>0.05). The proliferation of proximal tubular epithelial cells showed a significant change 96 h after the culture and the cellular proliferation induced by hepatocyte growth factor (HGF) was very active (P0.05), while 24 and 96 h after the culture, a persistent and significantly higher expression of c-met mRNA was found in HGF-induced proliferation. It is concluded that addition of exogenous HGF could inhibit the apoptosis induced by high-level glucose, promote the proliferation of proximal tubular epithelial cells, and induce the expression of c-met. Our study suggests that local up-regulation of HGF/c-met system plays an important role in the repair of renal damage in diabetic nephropathy.

Expression of c-met Stimulated by High Glucose in Human Renal Tubular Epithelial Cells and Its Implication / 华中科技大学学报（医学）（英德文版）

The expression of c-met stimulated by high glucose in human renal tubular epithelial cells and the role of HGF/c-met system in diabetic nephropathy were examined. The proximal tubular epithelial cells were cultured in vitro under different conditions. MTT was used for the detection of cellular proliferation and RT-PCR was employed for measurement of c-met mRNA level. Our results showed that under different conditions, there were no significant differences in the proliferation of proximal tubular epithelial cells 12 h and 24 h after the culuture (P＞0.05). The proliferation of proximal tubular epithelial cells showed a significant change 96 h after the culture and the cellular proliferation induced by hepatocyte growth factor (HGF) was very active (P＜0.05). Moreover, no significant difference in the expression of c-met mRNA was found 12 h after the culture under different conditions (P＞0.05), while 24 and 96 h after the culture, a persistent and significantly higher expression of c-met mRNA was found in HGF-induced proliferation. It is concluded that addition of exogenous HGF could inhibit the apoptosis induced by high-level glucose, promote the proliferation of proximal tubular epithelial cells, and induce the expression of c-met. Our study suggests that local up-regulation of HGF/c-met system plays an important role in the repair of renal damage in diabetic nephropathy.

Expression of resistin protein in abdominal and thigh subcutaneous adipose tissues / 中国组织工程研究

BACKGROUND: Resistin is an adipocyte-derived polypeptides. While central obesity can result in insulin resistance and type 2 diabetes mellitus.OBJECTIVE: To compare the expression of resistin protein in subcutaneous adipose tissue of normal human abdominal and thigh, and to investigate the role of resistin in central obesity bringing insulin resistance.DESIGN: Controlled observational experiment.SETTING: Department of Endocrinology, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology.PARTICIPANTS: Totally 20 patients hospitalized between January and April 2003 at the Department of Surgery of Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology were selected. All cases were divided into abdominal fat group with 12 cases and thigh fat group with 8 cases based on the site of fat tissue.METHODS: ①Blood pressure, height, body mass were measured and body mass index (BMI), percentage of body fat (BF%) in vivo (according to formulas induced by data from white people) were calculated: Male=1.2×body mass (kg)+height-2 (M-2)+0.23×age-16.2; Female =1.2× body mass (kg)×height-2 (m-2)+0.23×age-5.4. ②Fasting blood glucose was measured with glucose oxidase assay. ③Protein was isolated with lysis buffer and protein concentration was identified with Bradford method; The expression of resistin protein was measured with Western-blot method.MAIN OUTCOME MEASURES: Blood pressure, BMI, BF%; fasting blood glucose and expression of resistin protein of all cases of the two groups.RESULTS: Totally 20 patients were involved the result analysis. ①There were no significant difference in fast blood glucose, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI) and BF%between two groups (P ＞ 0.05). ②Expression levels (A) of resistin protein in abdominal subcutaneous adipose tissues was (14 942±6 076), which was more higher than that in thigh subcutaneous adipose tissues (39 421±6 087). There was markedly significant difference (P ＜ 0.01).CONCLUSION: The expression of resistin protein is much greater in abdominal fat depots than in thigh fat depots, which has evaluative value for studying the episode of central obesity-induced insulin resistance and type 2 diabetes mellitus.

Expression of Resistin Protein in Normal Human Subcutaneous Adipose Tissue and Pregnant Women Subcutaneous Adipose Tissue and Placenta / 华中科技大学学报（医学）（英德文版）

The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta and the relationship between obesity, type 2 diabetes mellitus (T2DM), pregnant physiological insulin resistance (IR) and gestational diabetes mellitus (GDM) was investigated. The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta was detected by using Western blotting method.Fasting serum glucose concentration was measured by glucose oxidase assay. Serum cholesterol (CHOL), serum triglycerides (TG), serum HDL cholesterol (HDL-C) and serum LDL cholesterol (LDL-C) were determined by full automatic biochemical instrument. Fasting insulin was measured by enzyme immunoassay to calculate insulin resistance index (IRI). Height, weight, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured to calculate body mass index (BMI) and body fat percentage (BF %). Resistin protein expression in pregnant women placental tissue (67 905±8441) (arbitrary A values) was much higher than that in subcutaneous adipose tissue in pregnant women abdomen (40 718 ± 3818, P ＜ 0.01), non-pregnant women abdomen (38 288±2084, P＜0.01), normal human abdomen (39 421±6087, P＜0.01)and thigh (14 942 ±6706, P＜0. 001) respectively. The resistin expression in abdominal subcutaneous adipose tissue showed no significant difference among pregnant, non-pregnant women and normal human, but much higher than that in thigh subcutaneous adipose tissue (P＜0. 001). Pearson analysis revealed that resistin protein was correlated with BMI (r=0.42), fasting insulin concentration (r=0.38),IRI (r=0. 34), BF % (r=0.43) and fasting glucose (r=0. 39), but not with blood pressure,CHOL, TG, HDL-C and LDL-C. It was suggested that resistin protein expression in human abdominal subcutaneous adipose tissue was much higher than that in human thigh subcutaneous adipose tissue. Resistin was closely related with central obesity, leading to IR, subsequently obesity and T2DM. Resistin protein expression in placental tissue was much higher than that in subcutaneous adipose tissue in normal human abdomen, pregnant abdomen, non-pregnant women abdomen and thigh. It was indicated that resistin protein could be secreted from human placental tissue. Resistin might be one of the factors that lead to pregnant physiological IR and GDM.

Expression of resistin protein in normal human subcutaneous adipose tissue and pregnant women subcutaneous adipose tissue and placenta / 华中科技大学学报（医学）（英德文版）

The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta and the relationship between obesity, type 2 diabetes mellitus (T2DM), pregnant physiological insulin resistance (IR) and gestational diabetes mellitus (GDM) was investigated. The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta was detected by using Western blotting method. Fasting serum glucose concentration was measured by glucose oxidase assay. Serum cholesterol (CHOL), serum triglycerides (TG), serum HDL cholesterol (HDL-C) and serum LDL cholesterol (LDL-C) were determined by full automatic biochemical instrument. Fasting insulin was measured by enzyme immunoassay to calculate insulin resistance index (IRI). Height, weight, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured to calculate body mass index (BMI) and body fat percentage (BF %). Resistin protein expression in pregnant women placental tissue (67 905 +/- 8441) (arbitrary A values) was much higher than that in subcutaneous adipose tissue in pregnant women abdomen (40 718 +/- 3818, P < 0.01), non-pregnant women abdomen (38 288 +/- 2084, P < 0.01), normal human abdomen (39 421 +/- 6087, P < 0.01) and thigh (14 942 +/- 6706, P < 0.001) respectively. The resistin expression in abdominal subcutaneous adipose tissue showed no significant difference among pregnant, non-pregnant women and normal human, but much higher than that in thigh subcutaneous adipose tissue (P < 0.001). Pearson analysis revealed that resistin protein was correlated with BMI (r = 0.42), fasting insulin concentration (r = 0.38), IRI (r = 0.34), BF % (r = 0.43) and fasting glucose (r = 0.39), but not with blood pressure, CHOL, TG, HDL-C and LDL-C. It was suggested that resistin protein expression in human abdominal subcutaneous adipose tissue was much higher than that in human thigh subcutaneous adipose tissue. Resistin was closely related with central obesity, leading to IR, subsequently obesity and T2DM. Resistin protein expression in placental tissue was much higher than that in subcutaneous adipose tissue in normal human abdomen, pregnant abdomen, non-pregnant women abdomen and thigh. It was indicated that resistin protein could be secreted from human placental tissue. Resistin might be one of the factors that lead to pregnant physiological IR and GDM.

The Influence of the Pro12Ala Mutation of PPARγ2 Receptor Gene on β-cells Restoration and Insulin Resistance in Type 2 Diabetes with Hypertension / 华中科技大学学报（医学）（英德文版）

The aim of this investigation was to determine whether a PPARγ2 Pro12Ala polymorphism was associated with insulin resistance, β-cell function and hypertension in Chinese populations. 289 unrelated Chinese subjects first diagnosed Type 2 diabetes (HbAC1＜6.0) were investigated, including 132 hypertensive diabetic (HTD) subjects, 157 normotensive diabetic (NTD) subjects. Blood pressure and anthropometric measurements were collected from all participants, as well as several venous blood samples during oral glucose tolerance test (OGTT). Biochemical measurements (high-density lipoprotein (HDL) and low-density lipoprotein-cholesterol (LDL), triglycerides) and PPARγ2 Pro12Ala genotype were also determined. And insulin resistance and β-cells function was assessed by HOMA-IR and HOMA-β respectively. The frequency of subjects bearing the Pro12Ala was lower in the hypertension group (3.03 %) than in the non-hypertension group (5.7 %) (P＜0.05) after adjusted for age, BMI and gender. Hypertensive diabetic Pro12Ala subjects had lower fasting plasma glucose level (P=0. 0127), and better glucose tolerance 60 min after oral glucose (P=0. 0361). Moreover, plasma insulin concentrations at 60 min was lower than those without A variant (P = 0. 0275), and both hypertensive Ala/Pro in HOMA-β (P = 0. 0455) and AUC for insulin (P=0. 0473) were higher, and HOMA-IR was lower (P=0. 0375) as compared with hypertensive Pro/Pro subjects. No association was observed between Pro12Ala genotype and BMI, total cholesterol, HDL- cholesterol or triglycerides in either group. Our findings suggested that the Ala 12 allele of the PPARγ2 gene may improve insulin resistance and ameliorate β-cell function reserves in T2DM with hypertension, and protect patients from hypertension in T2DM. As an important thrifty gene, environment factors may exerts an effect of PPAR γ2 on glucose homeostasis and insulin resistance.

Effect of Tumor Necrosis Factor-α on Resistin Expression in 3T3-L1 Adipocytes and Its Mechanism / 华中科技大学学报（医学）（英德文版）

In order to investigate the effect of tumor necrosis factor-α (TNFα) on resistin expression in 3T3-L1 adipocytes, and further explore its mechanisms, the differentiated 3T3-L1 adipocytes were incubated with 0, 1, 10, 100 ng/mL TNFα respectively for 24 h, and then the expression of resistin was determined. The differentiated 3T3-L1 adipocytes were incubated with 100 ng/mL TNFα for 3, 6, 24 h respectively, and then the expression of resistin mRNA was analyzed.3T3-L1 adipocytes were induced to differentiate into mature adipocytes. The cells were randomly divided into 4 groups for culture. In the control group, no drugs were added. Cells of TNFα group were treated with 100 ng/mL TNFα. In Ro-31-8220 group, 5μmol/L protein kinase C inhibitor Ro-31-8220 was added. With TNFα+Ro-31-8220 group, 100 ng/mL TNFα were added 1 h after the addition of 5 μmol/L Ro-31-8220. All adipocytes were cultured for 24 h. Reverse transcriptionpolymerase chain reaction (RT-PCR) and Western blotting were employed to detect the expression of resistin gene. Our results showed that resistin protein and mRNA in 3T3-L1 adipocytes were inhibited by TNFα at different concentrations (P＜0.01), and the inhibitory effect increased with the concentration (P＜0.01). At the same concentrations, the inhibitory effect increased with time (P ＜0.01). Ro-31-8220 could inhibit its expression and the inhibitive effect remained unchanged with addition of TNFα(P＞0.05). It was concluded that TNFα could inhibit the expression of resistin in 3T3-L1 adipocytes. The mechanism may be that the expression of resistin is partly controlled by protein kinase C signal conduction pathway.

The influence of the Pro12Ala mutation of PPARgamma2 receptor gene on beta-cells restoration and insulin resistance in type 2 diabetes with hypertension / 华中科技大学学报（医学）（英德文版）

The aim of this investigation was to determine whether a PPARgamma2 Pro12Ala polymorphism was associated with insulin resistance, beta-cell function and hypertension in Chinese populations. 289 unrelated Chinese subjects first diagnosed Type 2 diabetes (HbAC1 < 6.0) were investigated, including 132 hypertensive diabetic (HTD) subjects, 157 normotensive diabetic (NTD) subjects. Blood pressure and anthropometric measurements were collected from all participants, as well as several venous blood samples during oral glucose tolerance test (OGTT). Biochemical measurements (high-density lipoprotein (HDL) and low-density lipoprotein-cholesterol (LDL), triglycerides) and PPARgamma2 Pro12Ala genotype were also determined. And insulin resistance and beta-cells function was assessed by HOMA-IR and HOMA-beta respectively. The frequency of subjects bearing the Pro12Ala was lower in the hypertension group (3.03%) than in the non-hypertension group (5.7%) (P < 0.05) after adjusted for age, BMI and gender. Hypertensive diabetic Pro12Ala subjects had lower fasting plasma glucose level (P = 0.0127), and better glucose tolerance 60 min after oral glucose (P = 0.0361). Moreover, plasma insulin concentrations at 60 min was lower than those without A variant (P = 0.0275), and both hypertensive Ala/Pro in HOMA-beta (P = 0.0455) and AUC for insulin (P = 0.0473) were higher, and HOMA-IR was lower (P = 0.0375) as compared with hypertensive Pro/Pro subjects. No association was observed between Pro12Ala genotype and BMI, total cholesterol, HDL- cholesterol or triglycerides in either group. Our findings suggested that the Ala 12 allele of the PPARgamma2 gene may improve insulin resistance and ameliorate beta-cell function reserves in T2DM with hypertension, and protect patients from hypertension in T2DM. As an important thrifty gene, environment factors may exerts an effect of PPAR gamma2 on glucose homeostasis and insulin resistance.

The effect of rosiglitazone on resistin mRNA expression in type 2 diabetic rats / 中国糖尿病杂志

The STZ- and high fat diet-induced diabetic rats treated with rosiglitazone had lower FBG, fasting insulin, and serum cholesterol, and higher insulin sensitiviby index compared with (non-treatment) diabetic rats.

Protective effects of 3-aminobenzamide on kidney in diabetic rats / 中国医师杂志

Objective To investigate the protective effects of 3-aminobenzamide on the kidney of STZ-induced diabetic rats.Methods Experimental rats were divided into normal control group(group NC),diabetic control group(group DC) and diabetic rats treated with 3-aminobenzamide(group DT).The indexes such as the creatinine clearance rate(Ccr),the ratio of kidney weight to body weight,the contents of blood glucose,24h urinary protein,malonaldehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px) were tested in each group after 4 weeks.The expression of PARP was tested by immunohistochemistry method.Results Compared with group DC,the 24h urinary protein,Ccr and the concentration of MDA were decreased in group DT,as well as the activity of SOD and GSH-Px was enhanced(all P

Effect of protein kinase C signal pathway on resistin expression in 3T3-L1 adipocytes / 中国病理生理杂志

AIM: To investigate the effect of protein kinase C on resistin expression in 3T3-L1 adipocytes.METHODS: The differentiated 3T3-L1 adipocytes were incubated with 50 nmol/L phorbol 12-myristate 13-acetate(PMA) or(5 ?mol/L) Ro-31-8220 for 24 h.Expression of resistin mRNA was detected by RT-PCR and expression of resistin protein was detected by Western blotting.RESULTS: Compared with control,PMA increased the expression of resistin mRNA and protein in 3T3-L1 adipocytes significantly(P

Expression and distribution of VLDLR and its subtypes in various tissues of type 2 diabetic rat / 中国糖尿病杂志

Objective To investigate the distribution and expression of total amount and two subtypes of very low density lipoprotein receptor(VLDLR)in various tissues(heart,cerebrum,kidney,muscle,adipose)of normal SD rats and type 2 diabetic SD rats.Methods The mRNA of VLDLR from various tissues were amplified by semi-quantitative RT-PCR.Results The expression levels of VLDLR were reduced in all collected tissues compared with normal ones,especially in cerebrum,kidney,muscle,adipose(P