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

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.

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.

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.

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

Objective To investigate the dysfunction of gallbladder emptying in diabetic patients and its possible mechanism. Methods The postprandial gallbladder emptying function and the release of pancreatic polypeptide (PP), as well as the therapeutic effect of Cisapride on gallbladder contraction were observed in 50 diabetics without cholecystolithiasis and 15 normal controls. The distributions of nitric oxide synthase (NOS) and acetylcholinesterase (AChE) in the wall of surgical removal gallbladders of 7 diabetic patients with cholecystolithiasis were also studied by histochemistry method. Results (1) The function of gallbladder emptying was distinctly lower in diabetic patients with autonomic neuropathy (AN) than that of the healthy subjects and diabetic patients without AN (NAN). (2) The postprandial release of PP in AN group was significantly lower than those in NAN group and healthy subjects. (3) The gallbladder emptying function was improved after receiving Cisapride in patients with AN. (4) Both the amount and activity of NOS and AChE in the wall of gallbladders of diabetic patients were lower than that of the non-diabetic subjects. Conclusion The dysfunction of gallbladder emptying in diabetic patients is partly due to the impaired autonomic nerve. The administration of Cisapride will improve the gallbladder emptying function of diabetic patients with AN.

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.
Alanine/genetics ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/*genetics ; Genetic Predisposition to Disease ; Hypertension/*complications ; Hypertension/genetics ; Insulin Resistance/*genetics ; Insulin-Secreting Cells/*physiology ; Mutation ; PPAR gamma/*genetics ; Proline/genetics

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

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.

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.