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Articles by Y. Zhang
Total Records ( 22 ) for Y. Zhang
  Y Wang , F Meng and Y. Zhang
 

The low-molecular-weight protein tyrosine phosphatases (PTPase) exist ubiquitously in prokaryotes and eukaryotes and play important roles in the regulation of physiological activities. We report here the expression, purification and characterization of an active and soluble PTPase from Thermus thermophilus HB27 in Escherichia coli. This PTPase has an optimum pH range of 2.8–4.8 when using p-nitrophenyl phosphate as the substrate. The thermal inactivation results indicate a high thermal stability of this enzyme, with the optimum temperature of 75°C for activity. It can be activated by Mn2+, Mg2+, Ca2+, Ba2+, and Ni2+, but inhibited by Zn2+, Cu2+, Cl, and SO42–. These results suggest that this heat-resistant PTPase may play important roles in vivo in the adaptation of the microorganism to extreme temperatures and specific nutritional conditions.

  L Zhang , Q Liu , Y Zhou and Y. Zhang
 

The male reproductive tracts in different species are characterized by similar patterns of male-dependent overexpression of carboxylesterases. This phenomenon indicates male sex-associated functions of these enzymes for spermatogenesis, sperm maturation, and sperm use. Recently, a novel epididymis-specific gene named Ces7 was cloned and characterized, which belongs to the carboxylesterase family. To study the functions of CES7 in sperm maturation and storage, CES7 recombinant protein was expressed in baculovirus system. The recombinant protein had carboxylesterase activity hydrolyzing cholesterol ester and choline ester. CES7 as carboxylesterase might be involved in ester hydrolysis, sperm maturation, and storage in male reproductive tract.

  L Zhang , Z Hu , C Zhu , Q Liu , Y Zhou and Y. Zhang
 

Carboxylesterases (CEs) represent a multigene family of serine-dependent enzymes. Male-dependent CEs are over-expressed in the male reproductive tract of different animal species (bivalve mollusks, fruit-flies, and mammals). Here, a novel rat epididymis-specific gene named Ces7 was cloned and characterized. It was a novel member of CE family, which was mainly expressed and secreted to the lumens of the corpus and cauda epididymis. CES7 protein was highly glycosylated as other mammalian CEs. Furthermore, Ces7 increased with age growth until sex maturation and then maintained at high level. CES7 might be one of the major CEs in male reproductive tract and contribute to the sperm fertilization.

  J Lan , S Hua , X He and Y. Zhang
 

In mammals, DNA methylation, characterized by the transfer of the methyl group from S-adenosylmethionines to a base (mainly referred to cytosine), acts as a major epigenetic modification. In parallel to DNA sequences arrangement, modification of methylation to DNA sequences has far-reaching influence on biological functions and activities, for it involves controlling gene transcription, regulating chromatin structure, sustaining genome stability and integrity, maintaining parental imprinting and X-chromosome inactivation, suppressing homologous recombination as well as limiting transposable elements, during which DNA methyltransferases (DNMTs) and methyl-binding proteins play important roles. Their aberrance can give rise to dysregulation of gene expression, cell maltransformation and so on. Hence, it is necessary to gain a good understanding of these two important kinds of proteins, which will help to better investigate the epigenetic mechanisms and manipulate the modifications according to our will based on its reversibility. Here we briefly review our current understanding of DNMTs and methyl-binding proteins in mammals.

  A Bhattacharya , L Tang , Y Li , F Geng , J. D Paonessa , S. C Chen , M. K.K Wong and Y. Zhang
 

Bladder cancer is one of the common human cancers and also has a very high recurrence rate. There is a great need for agents capable of inhibiting bladder cancer development and recurrence. Here, we report that allyl isothiocyanate (AITC), an ingredient of many common cruciferous vegetables, potently inhibited the proliferation of bladder carcinoma cell lines in vitro [half maximal inhibitory concentration (IC50) of 2.7–3.3 µM], which was associated with profound G2/M arrest and apoptosis. In contrast, AITC was markedly less toxic to normal human bladder epithelial cells (IC50 of 69.4 µM). AITC was then evaluated in two rat bladder cancer models in vivo (an orthotopic model and a subcutaneous model). The orthotopic model closely mimics human bladder cancer development and recurrence. We show that a low oral dose of AITC (1 mg/kg) significantly inhibited the development and muscle invasion of the orthotopic bladder cancers but was ineffective against the subcutaneous xenografts of the same cancer cells in the same animals. This differential effect was explained by our finding that urinary levels of AITC equivalent were two to three orders of magnitude higher than that in the plasma and that its levels in the orthotopic cancer tissues were also three orders of magnitude higher than that in the subcutaneous cancer tissues. Moreover, we show that AITC is a multi-targeted agent against bladder cancer. In conclusion, AITC is selectively delivered to bladder cancer tissue through urinary excretion and potently inhibits bladder cancer development and invasion.

  Y Ding , J. D Paonessa , K. L Randall , D Argoti , L Chen , P Vouros and Y. Zhang
 

Sulforaphane (SF) is a well-known chemopreventive phytochemical and occurs in broccoli and to a lesser extent in other cruciferous vegetables, whereas 4-aminobiphenyl (ABP) is a major human bladder carcinogen and is present at significant levels in tobacco smoke. Here, we show that SF inhibits ABP-induced DNA damage in both human bladder cells in vitro and mouse bladder tissue in vivo, using dG-C8-ABP as a biomarker, which is the predominant ABP-DNA adduct formed in human bladder cells and tissues. SF activates NF-E2 related factor-2 (Nrf2), which is a well-recognized chemopreventive target and activates the Nrf2-regulated cytoprotective signaling pathway. Comparison between wild-type mice and mice without Nrf2 shows that Nrf2 activation is required by SF for inhibition of ABP-induced DNA damage. Moreover, Nrf2 activation by SF in the bladder occurs primarily in the epithelium, which is the principal site of bladder cancer development. These data, together with our recent observation that SF-enriched broccoli sprout extracts strongly inhibits N-butyl-N-(4-hydroxybutyl)nitrosamine-induced bladder cancer development, suggest that SF is a highly promising agent for bladder cancer prevention and provides a mechanistic insight into the repeated epidemiological observation that consumption of broccoli is inversely associated with bladder cancer risk and mortality.

  A Bhattacharya , Y Li , K. L Wade , J. D Paonessa , J. W Fahey and Y. Zhang
 

Allyl isothiocyanate (AITC), which occurs in many common cruciferous vegetables, was recently shown to be selectively delivered to bladder cancer tissues through urinary excretion and to inhibit bladder cancer development in rats. The present investigation was designed to test the hypothesis that AITC-containing cruciferous vegetables also inhibit bladder cancer development. We focused on an AITC-rich mustard seed powder (MSP-1). AITC was stably stored as its glucosinolate precursor (sinigrin) in MSP-1. Upon addition of water, however, sinigrin was readily hydrolyzed by the accompanying endogenous myrosinase. This myrosinase was also required for full conversion of sinigrin to AITC in vivo, but the matrix of MSP-1 had no effect on AITC bioavailability. Sinigrin itself was not bioactive, whereas hydrated MSP-1 caused apoptosis and G2/M phase arrest in bladder cancer cell lines in vitro. Comparison between hydrated MSP-1 and pure sinigrin with added myrosinase suggested that the anticancer effect of MSP-1 was derived principally, if not entirely, from the AITC generated from sinigrin. In an orthotopic rat bladder cancer model, oral MSP-1 at 71.5 mg/kg (sinigrin dose of 9 µmol/kg) inhibited bladder cancer growth by 34.5% (P < 0.05) and blocked muscle invasion by 100%. Moreover, the anticancer activity was associated with significant modulation of key cancer therapeutic targets, including vascular endothelial growth factor, cyclin B1 and caspase 3. On an equimolar basis, the anticancer activity of AITC delivered as MSP-1 appears to be more robust than that of pure AITC. MSP-1 is thus an attractive delivery vehicle for AITC and it strongly inhibits bladder cancer development and progression.

  X. K. Zhang , Y. G. Xiao , Y. Zhang , X. C. Xia , J. Dubcovsky and Z. H. He
  Information on the distribution of vernalization genes and their association with growth habit is crucial to understanding the adaptability of wheat (Triticum aestivum L.) cultivars to different environments. In this study, 278 Chinese wheat cultivars were characterized with molecular markers for the vernalization genes Vrn-A1, -B1, -D1, and -B3. Heading time was evaluated in a greenhouse under long days without vernalizaton. The dominant Vrn-D1 allele showed the highest frequency in the Chinese wheat cultivars (37.8%), followed by the dominant Vrn-A1, -B1, and -B3 alleles. Ninety-two winter cultivars carried recessive alleles of all four vernalization loci, whereas 172 spring genotypes contained at least one dominant Vrn allele. All cultivars released in the North China Plain Winter Wheat Zone were winter type. Winter (53.0%), spring (36.1%), and early-heading (10.9%) cultivars were grown in the Yellow and Huai River Valley Winter Zone. Most of the spring genotypes from this zone carried only the dominant Vrn-D1 allele, which was also predominant (64.1%) in the Middle and Lower Yangtze Valley Winter Zone and Southwestern Winter Wheat Zone. In three spring-sown wheat zones, all cultivars were early-heading spring types that frequently possessed the strongest dominant Vrn-A1a allele and combinations with other dominant Vrn gene(s). The Vrn-D1 allele is associated with the latest heading time, Vrn-A1 the earliest, and Vrn-B1 intermediate values. The information is important for breeding programs in countries interested in using Chinese wheats.
  Y. Zhang , A. Vitry , E. Roughead , P. Ryan and A. Gilbert
  Objective To examine the impact of co-morbidity on health service utilization by Australian veterans with diabetes.
Methods A retrospective cohort study was undertaken including veterans aged ≥ 65 years dispensed medicines for diabetes in 2006. Data were sourced from the Australian Department of Veterans' Affairs health claims database. Utilization of preventive health services for diabetes was assessed, including claims for glycated haemoglobin (HbA1c) test, microabuminuria, podiatry services, diabetes care plans, medication reviews, case conferences, general practitioner (GP) management plans and ophthalmology/optometry services.
Results Among the 17 095 veterans dispensed medicines for diabetes, more than 80% had four or more co-morbid conditions. Those with a higher number of co-morbidities were more likely to have had claims for optometry/ophthalmology services and podiatry services, but not for other services. Veterans with at least one diabetes-related hospital admission had no more claims for diabetes health services than those who had no diabetics-related hospital admission, except for endocrinology services (relative risk = 1.26, 95% confidence intervals 1.15–1.37). Veterans with dementia were less likely to have had claims for diabetes health services while patients with renal failure were more likely to have had claims for the services.
Conclusions Low utilization of preventive diabetes care services is apparent in all co-morbidity groups. Patients with renal failure or dementia used more and less health services resources, respectively. Given the high mean age of this population, there may be valid reasons for the low use, such as competing health demands and patients' preferences.
  Z. Li , S. M. Henning , Y. Zhang , N. Rahnama , A. Zerlin , G. Thames , C. H. Tseng and D. Heber
 

Aims

Consumption of a high-fat diet has been demonstrated to promote endothelial dysfunction, possibly through an increase in lipid peroxidation and decrease in serum nitric oxide. The present study was designed to investigate whether consumption of a hamburger cooked with a polyphenol-rich spice mixture will reduce postprandial lipid oxidation and endothelial dysfunction in men with Type 2 diabetes.

Methods

Twenty-two subjects consumed burgers cooked with salt only (control burger) or with salt and spice mix (spice burger) in randomized order. The postprandial concentration of urinary malondialdehyde and nitrate/nitrite as well as the peripheral arterial tonometry score were determined.

Results

Eighteen subjects completed the study. Postprandial serum glucose, insulin and triglyceride concentrations were similar in all subjects after control burger or spice burger consumption. Urine malondialdehyde excretion in mmol/g creatinine was reduced by 31% (P < 0.001) after consuming the spice burger compared with the control burger. Two hours after consumption of the burgers, the peripheral arterial tonometry score was significantly different between control burger consumption (−9.7 ± 21.5%) and spice burger consumption (+18.0 ± 42.4%) (P = 0.025). Mean urinary nitrate/nitrite concentrations in urine collected during the 6 h after consumption of the control burger was 9.09 ± 5.7 mmol/g creatinine, but 12.37 ± 7.00 mmol/g creatinine after the spice burger (P = 0.053).

Conclusion

Adding a spice mix to hamburger meat prior to cooking resulted in a reduction in urinary malondialdehyde, an increase in urinary nitrate/nitrite and improvement of postprandial endothelial dysfunction in men with Type 2 diabetes. Therefore, cooking a hamburger with a polyphenol-rich spice mixture may lead to potential cardiovascular benefits in patients with Type 2 diabetes mellitus.

  W. Gu , Y. Huang , Y. Zhang , J. Hong , Y. Liu , W. Zhan , G. Ning and W. Wang
 

Aim

To compare the carotid intima-media thickness in patients with newly diagnosed Type 1 or Type 2 diabetes ranging from 14 to 30 years of age.

Methods

Demographic, anthropometric and laboratory data were obtained from 404 adolescents and young adults (103 subjects with Type 1 diabetes, 94 with Type 2 diabetes, 153 obese subjects and 54 normal control subjects). Carotid intima-media thickness was assessed based on Doppler ultrasound examination and compared among the four groups.

Results

Our data showed significant increases in carotid intima-media thickness in subjects with Type 1 diabetes, Type 2 diabetes and obese subjects compared with the control subjects, with those in the group with Type 2 diabetes demonstrating the greatest change (P < 0.001). Age, BMI, percentage of fat, waist-hip ratio and total triglycerides were significantly correlated with both common and internal carotid intima-media thickness segments. From a stepwise multiple linear regression model, the independent determinants of common carotid intima-media thickness were age, BMI, HbA1c and HDL cholesterol (adjusted R2 = 0.152, P < 0.001). After adjustment for age, sex and HbA1c, the odds ratio for increased carotid intima-media thickness was 1.67 (95% CI 1.19-2.33, P = 0.003) for obese subjects, 2.38 (95% CI 1.59-9.47, P = 0.001) for subjects with Type 1 diabetes and 3.93 (95% CI 1.90-6.07, P = 0001) for subjects with Type 2 diabetes compared with the control subjects.

Conclusions

Compared with young control subjects, we found significant increases in carotid intima-media thickness in patients with newly diagnosed Type 1 diabetes and Type 2 diabetes, with patients with Type 2 diabetes showing greater carotid intima-media thickness. Traditional cardiovascular risk factors, such as obesity, dyslipidaemia, hypertension and hyperglycaemia, could cause vessel changes even in adolescents and young adults.

  Y. Zhang and B. Feng
  This study propose a new method based on Formal Concept Analysis (FCA) to group and organize search results. After formal concepts are extracted using FCA, the concepts most relevant to the query are selected and extracted and then a two-level hierarchy is built and presented to the user. We refer the proposed algorithm to as CHC (Conceptual and Hierarchical Clustering). Evaluating the quality of the clustering results is a non-trivial task. Two improved objective metrics of clustering quality, ANCE@K and ANCE@K, are proposed based on NMI (normalized mutual information) and NCE (normalized complementary entropy) metrics but eliminating the biases existed in them. We compare CHC with three other Search Results Clustering (SRC) algorithms: Suffix Tree Clustering (STC), Lingo and Vivisimo, using a comprehensive set of documents obtained from the Open Directory Project hierarchy as benchmark. In addition to comparison based on objective measures, we also subjectively analyze the properties of cluster labels produced by different SRC algorithms. The experimental results show that our method outperforms the other three SRC algorithms and is helpful to the user for browsing and locating the results of interests.
  F.A. Mianji , Y. Zhang and A. Babakhani
  The study categorizes the most frequent researched areas of resolution enhancement in hyperspectral imagery and emphasizes on their applications, requirements, achievements and limitations of different approaches. An evaluation of the capabilities of different classes of super-resolution algorithms in hyperspectral imagery shows that there is no generic approach to optimally produce high-quality results on general hyperspectral images and the adequacy of an algorithm is a function of multiple factors, namely, access to multisource information, computational complexity, availability of reliable training data for learning-based methods, efficiency of the algorithm and the expected application. It is also shown that spectral mixture analysis based techniques are appropriate for developing high performance and fast super-resolution algorithms in hyperspectral imagery.
  G.S. Hu , G.B. Chang , Y. Zhang , J. Hong , Y. Liu and G.H. Chen
  The present research was to study the association of polymorphism of Natural resistance-associated macrophage protein1 (Nramp1) with some immune functions in Rugao chicken (RG) and Recessive White chicken (RW). The PCR-SSCP technique was applied to analyze the correlation between the polymorphisms of Nramp1 gene and immune functions (Heterophil/Lymphocyte (H/L), lymphocyte transformation rate and the content of IgM) in 72 RG and 55 RW. The results showed that: the Heterophil/Lymphocyte (H/L), lymphocyte transformation rate and the content of IgM in RG and RW showed significant differences (p<0.05). H/L of AA was significantly lower than BB and AB while the AA’s lymphocyte transformation rate and IgM were significantly higher than the BB’s in both RG and RW. The results demonstrated that the general immune performances of RG were superior to those of RW. The general immune performances of AA were superior to BB and AB.
  J. Hong , J.G. Dai , W.T. Guan , G. Jin , Zh.L. Huang , L.J. Zhang , J. Zh. Dang and Y. Zhang
  Tachyplesin I is a 17 amino acid cationic antibacterial peptide with a typical cyclic antiparallel β-sheet structure. It is not clear whether tachyplesin I can induce resistance in bacteria. Therefore, two selection procedures by gradually increasing the induction concentration of tachyplesin I were performed to determine whether tachyplesin I could induce resistance in Escherichia coli and Staphylococcus aureus in vitro. The results showed that tachyplesin I did not induce resistance in Escherichia coli ATCC25922, F41 and Staphylococcus aureus ATCC25923 in this study whereas high resistance to benzylpenicillin was induced using the same procedures in Staphylococcus aureus ATCC25923. Furthermore, no cross-resistance between tachyplesin I and benzylpenicillin was observed. It is suggested that tachyplesin I may be a safe antibacterial agent for future use in clinical practice.
  Y. Zhang , H.X. Zheng , Z.D. Zhang , Y. Jin , F. Yang , J.J. He , W.J. Cao , D.H. Sun and L. Lv
  Field isolates of Foot-and-Mouth Disease Virus (FMDV) were found to use four αυ integrins (αυβ1, αυβ3, αυβ6 and αυβ8) as cellular receptors. Researchers established a stable Chinese Hamster Ovary clone K1 (CHO-K1) cell line expressing the murine αυβ1 heterodimer (designated as CHO-K1-αυβ1) using a highly efficient lentiviral-based gene transfer technology to deliver murine αυ, Internal Ribosome Entry Site (IRES) and β1 genes into cell chromosomes and the inserted genes were then transcribed from a Cytomegalovirus (CMV) promoter. αυβ1 expression was stringently regulated by Doxycycline (Dox) and was found to be stable. CHO-K1-αυβ1 cells were susceptible to FMDV type Asia l/HN/2006. The plaque assay revealed that the virus produced bigger and more plaques in CHO-K1-αυβ1 cells (1.05x104 PFU mL-1) than in CHO-K1 cells. When sodium heparin (1 and 2 mg mL-1) was used as the inhibitor, the number of plaques in CHO-K1 cells were significantly decreased (4.0x103-35 and 20 PFU mL-1), supported by time-course of replication and proliferation. The number and size of plaques on CHO-K1-αυβ1 cells showed no obvious change, indicating that the αυβ1 heterodimer expressed on CHO-K1-αυβ1 can be used as an FMDV receptor.
  Z.X. Cao , Z.H. Shi , Y. Zhang , Z. Chao , L.M. Wei , Q.W. Liu , X. Zhang , B.G. Ye , X.L. Zheng , F. Wang and Z.M. Lin
  Porcine Circovirus type 2 (PCV2) is one of the most important swine pathogens of economic importance. To understand the genetic diversity of Porcine Circovirus type 2 (PCV2) in South China, 49 PCV2 sequences from South China were compared to 58 other references sequences. Researchers found that the nucleotide similarity among all South China isolates ranged from 93.7-100%. Most of them were classified into PCV2b-1A/1B cluster but the rest mapped to clusters PCV2b-1C, PCV2a-2E or PCV2a-2F. The data contribute to the understanding of molecular variation of PCV2 in South China.
  F. Zhang , Y. Zhang , Jun Liu and Hanbin Luo
  Safety culture plays an important role in enterprise safety production. The paper analyzed the factors of real estate enterprise safety culture construction and then designed the questionnaire and did research on real estate enterprise safety culture. The questionnaire consists of workers’ information and seven safety culture dimensions, including safety management system level, publicity and education training level, security issues and management participation level, employee safety consciousness level, staff safety knowledge and skill level, co-workers behavior influence level, as well as responsibility, rewards and pulishment level. Through analyzing the data of the questionnaire and combining it with the safety culture maturity model, the paper concludes that real estate enterprises safety culture is in the second gradient, with the safety culture in a primary stage. Enterprises need to encourage employees to participate in construcing and improving the level of enterprise safety culture. The article puts forward some measures for the improvement of the safety culture construction and some suggestions from the perspective of material, system, spirit and culture.
  S. C Wu and Y. Zhang
 

Nuclear hormone receptors (NRs) are transcription factors responsible for mediating the biological effects of hormones during development, metabolism, and homeostasis. Induction of NR target genes is accomplished through the assembly of hormone-bound NR complexes at target promoters and coincides with changes in histone modifications that promote transcription. Some coactivators and corepressors of NR can enhance or inhibit NR function by covalently modifying histones. One such modification is methylation, which plays important roles in transcriptional regulation. Histone methylation is catalyzed by histone methyltransferases and reversed by histone demethylases. Recent studies have uncovered the importance of these enzymes in the regulation of NR target genes. In addition to histones, these enzymes have nonhistone substrates and can methylate and demethylate NRs and coregulatory proteins in order to modulate their function. This review discusses recent progress in our understanding of the role of methylation and demethylation of histones, NRs, and their coregulators in NR-mediated transcription.

  S Hu , G Yao , X Guan , Z Ni , W Ma , E. M Wilson , F. S French , Q Liu and Y. Zhang
 

Epididymal function depends on androgen signaling through the androgen receptor (AR), although most of the direct AR target genes in epididymis remain unknown. Here we globally mapped the AR binding regions in mouse caput epididymis in which AR is highly expressed. Chromatin immunoprecipitation sequencing indicated that AR bound selectively to 19,377 DNA regions, the majority of which were intergenic and intronic. Motif analysis showed that 94% of the AR binding regions harbored consensus androgen response elements enriched with multiple binding motifs that included nuclear factor 1 and activator protein 2 sites consistent with combinatorial regulation. Unexpectedly, AR binding regions showed limited conservation across species, regardless of whether the metric for conservation was based on local sequence similarity or the presence of consensus androgen response elements. Further analysis suggested the AR target genes are involved in diverse biological themes that include lipid metabolism and sperm maturation. Potential novel mechanisms of AR regulation were revealed at individual genes such as cysteine-rich secretory protein 1. The composite studies provide new insights into AR regulation under physiological conditions and a global resource of AR binding sites in a normal androgen-responsive tissue.

  C. Liu , X. Wang , Z. Chen , L. Zhang , Y. Wu and Y. Zhang
 

Background: The effects of hepatic ischemia-reperfusion (I/R) on insulin signaling remain unclear. We observed changes in insulin secretion and signal protein expression during the early steps in insulin signaling after hepatic I/R in rats.

Materials and Methods: Eighty healthy Wistar rats were randomly divided into an I/R group and a control (C) group. After we exposed the hepatic hilum, ischemia was induced by clamping the hepatic artery and portal vein for 30 minutes and then the liver was reperfused for 2 hours in the I/R group; a show procedure was done in the C group. Blood samples were obtained after exposure of the hepatic hilum (T1) and 2 hours after reperfusion in the I/R group (T2) and 2.5 hours after T1 in the C group (T2). We measured glucose and insulin plasma concentrations. We determined the expressions of insulin signaling proteins, including insulin receptor (IR) β unit (IR β), IR substrate 1 (IRS-1), IRS-2, and P85 in phosphatidylinositol 3-kinase (PI3K) and tyrosine phosphorylation of these proteins in liver and skeletal muscle.

Results: Plasma glucose concentrations increased in both groups at T2 (P < .01) and were higher in the I/R group (P < .01). Insulin concentrations in the I/R group did not change significantly at T2. Insulin concentrations at T2 were higher than those at T1 in the C group (P < .05). Expressions of insulin signal proteins showed no significant difference between the 2 groups; however, tyrosine phosphorylation of IR β, IRS-1, IRS-2, and the interactions between IRS-1 in skeletal muscle or IRS-2 in liver and PI3K were significantly lower in the I/R group than the C group.

Conclusion: Hepatic I/R inhibited insulin secretion and induced insulin resistance via down-regulation during the early steps in insulin signaling in rats.
 
 
 
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