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Decreasing complexity of glucose time series derived from continuous glucose monitoring is correlated with deteriorating glucose regulation

《医学前沿（英文）》 2023年第17卷第1期页码 68-74 doi: 10.1007/s11684-022-0955-9

摘要： Most information used to evaluate diabetic statuses is collected at a special time-point, such as taking fasting plasma glucose test and providing a limited view of individual’s health and disease risk. As a new parameter for continuously evaluating personal clinical statuses, the newly developed technique “continuous glucose monitoring” (CGM) can characterize glucose dynamics. By calculating the complexity of glucose time series index (CGI) with refined composite multi-scale entropy analysis of the CGM data, the study showed for the first time that the complexity of glucose time series in subjects decreased gradually from normal glucose tolerance to impaired glucose regulation and then to type 2 diabetes (P for trend < 0.01). Furthermore, CGI was significantly associated with various parameters such as insulin sensitivity/secretion (all P < 0.01), and multiple linear stepwise regression showed that the disposition index, which reflects β-cell function after adjusting for insulin sensitivity, was the only independent factor correlated with CGI (P < 0.01). Our findings indicate that the CGI derived from the CGM data may serve as a novel marker to evaluate glucose homeostasis.

关键词： complexity of glucose time series continuous glucose monitoring impaired glucose regulation insulin secretion and sensitivity refined composite multi-scale entropy

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Inhibition of protein kinase B by Palmitate in the insulin signaling of HepG2 cells and the preventiveeffect of Arachidonic acid on insulin resistance

XIA Yanzhi, WAN Xuedong, DUAN Qiuhong, HE Shansu, WANG Ximing

《医学前沿（英文）》 2007年第1卷第2期页码 200-206 doi: 10.1007/s11684-007-0038-y

摘要： Elevated plasma levels of free fatty acids (FFAs) may contribute to insulin resistance (IR) that is characteristic of type 2 diabetes mellitus. In this study, we investigated the effects of two fatty acids, palmitate (PA) and arach

关键词： palmitate characteristic study plasma resistance

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Mechanism of insulin resistance in obesity: a role of ATP

《医学前沿（英文）》 2021年第15卷第3期页码 372-382 doi: 10.1007/s11684-021-0862-5

摘要： Obesity increases the risk of type 2 diabetes through the induction of insulin resistance. The mechanism of insulin resistance has been extensively investigated for more than 60 years, but the essential pathogenic signal remains missing. Existing hypotheses include inflammation, mitochondrial dysfunction, hyperinsulinemia, hyperglucagonemia, glucotoxicity, and lipotoxicity. Drug discoveries based on these hypotheses are unsuccessful in the development of new medicines. In this review, multidisciplinary literature is integrated to evaluate ATP as a primary signal for insulin resistance. The ATP production is elevated in insulin-sensitive cells under obese conditions independent of energy demand, which we have named “mitochondrial overheating.” Overheating occurs because of substrate oversupply to mitochondria, leading to extra ATP production. The ATP overproduction contributes to the systemic insulin resistance through several mechanisms, such as inhibition of AMPK, induction of mTOR, hyperinsulinemia, hyperglucagonemia, and mitochondrial dysfunction. Insulin resistance represents a feedback regulation of energy oversupply in cells to control mitochondrial overloading by substrates. Insulin resistance cuts down the substrate uptake to attenuate mitochondrial overloading. The downregulation of the mitochondrial overloading by medicines, bypass surgeries, calorie restriction, and physical exercise leads to insulin sensitization in patients. Therefore, ATP may represent the primary signal of insulin resistance in the cellular protective response to the substrate oversupply. The prevention of ATP overproduction represents a key strategy for insulin sensitization.

关键词： type 2 diabetes energy expenditure mitochondria hyperinsulinemia hyperglucagonemia AMPK

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Mechanisms of insulin resistance in obesity

null

《医学前沿（英文）》 2013年第7卷第1期页码 14-24 doi: 10.1007/s11684-013-0262-6

摘要：

Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that, there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy.

关键词： type 2 diabetes energy expenditure inflammation lipotoxicity mitochondria hyperinsulinemia adenosine monophosphate-activated protein kinase (AMPK)

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Insulin resistance and the metabolism of branched-chain amino acids

null

《医学前沿（英文）》 2013年第7卷第1期页码 53-59 doi: 10.1007/s11684-013-0255-5

摘要：

Insulin resistance (IR) is a key pathological feature of metabolic syndrome and subsequently causes serious health problems with an increased risk of several common metabolic disorders. IR related metabolic disturbance is not restricted to carbohydrates but impacts global metabolic network. Branched-chain amino acids (BCAAs), namely valine, leucine and isoleucine, are among the nine essential amino acids, accounting for 35% of the essential amino acids in muscle proteins and 40% of the preformed amino acids required by mammals. The BCAAs are particularly responsive to the inhibitory insulin action on amino acid release by skeletal muscle and their metabolism is profoundly altered in insulin resistant conditions and/or insulin deficiency. Although increased circulating BCAA concentration in insulin resistant conditions has been noted for many years and BCAAs have been reported to be involved in the regulation of glucose homeostasis and body weight, it is only recently that BCAAs are found to be closely associated with IR. This review will focus on the recent findings on BCAAs from both epidemic and mechanistic studies.

关键词： branched-chain amino acids leucine isoleucine valine insulin resistance

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Research on acoustic-structure sensitivity using FEM and BEM

ZHANG Jun, ZHAO Wenzhong, ZHANG Weiying

《机械工程前沿（英文）》 2007年第2卷第1期页码 62-67 doi: 10.1007/s11465-007-0010-1

摘要： Acoustic-structure sensitivity is used to predict the change of acoustic pressure when a structure design variable is changed. The sensitivity is significant for reducing noise of structure. Using FEM (finite element method) and BEM (boundary element method) acoustic-structure sensitivity was formulated and presented. The dynamic response and response velocity sensitivity with respect to structure design variable were carried out by using structural FEM, the acoustic response and acoustic pressure sensitivity with respect to structure velocity were carried out by using acoustic BEM. Then, acoustic-structure sensitivity was computed by linking velocity sensitivity in FEM and acoustic sensitivity in BEM. This method was applied to an empty box as an example. Acoustic pressure sensitivity with respect to structure thickness achieved in frequency ranges 1 100 Hz, and its change rule along with stimulating frequency and design variable were analyzed. Results show that acoustic-structure sensitivity method linked with FEM and BEM is effective and correct.

关键词： sensitivity method BEM acoustic pressure pressure sensitivity frequency

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Role of exercise training on insulin resistance and TNF-α in high-fat diet rats

Hui SUN MD, Xiuling DENG MM, Fangxi XIAO MD, Lulu CHEN MD, Huiqing LI MD,

《医学前沿（英文）》 2009年第3卷第4期页码 403-407 doi: 10.1007/s11684-009-0071-0

摘要： This study investigated the effect of exercise training on insulin resistance and serum and adipose TNF-α in high-fat diet-induced insulin-resistant rats. Thirty male Wistar rats were randomly divided into two groups: normal control group (NC; =8) that accepted normal chow and high-fat diet group (HF; =22) that fed on high-fat diet to induce insulin resistance model. The HF group was randomly assigned to two subgroups after 18 weeks: sedentary group (SE; =10) and exercise training group (ET; =12) that performed swimming exercise training for 6 weeks, while both groups continued high-fat diet. Changes of body weight, lipid profile, and fasting plasma glucose and insulin were measured. The insulin sensitivity index (ISI) was calculated. Serum concentration of TNF-α was detected by ELISA. The expression of TNF-α mRNA and protein in adipose tissue was examined by using real-time fluorescence quantitative polymerase chain reaction (PCR) and Western blot, respectively. After 18 weeks, compared with the NC group, body weight, blood lipid, glucose, and insulin in the HF group were significantly elevated, while the ISI decreased obviously, which suggested that insulin resistance appeared in the HF group. After exercise training for 6 weeks, compared with the SE group, both ISI and serum TNF-α concentration in the ET group were decreased significantly; however, the expression levels of TNF-α mRNA and protein in adipose tissue increased by 27.5% and 20.5%, respectively. In conclusion, exercise training ameliorates insulin resistance. The reduction of the level of serum TNF-α and the increased expression of TNF-α in adipose tissue by exercise training may be involved in this mechanism.

关键词： exercise training insulin resistance tumor necrosis factor-α

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Overcoming oral insulin delivery barriers: application of cell penetrating peptide and silica-based nanoporous

Huining HE, Junxiao YE, Jianyong SHENG, Jianxin WANG, Yongzhuo HUANG, Guanyi CHEN, Jingkang WANG, Victor C YANG

《化学科学与工程前沿（英文）》 2013年第7卷第1期页码 9-19 doi: 10.1007/s11705-013-1306-9

摘要： Oral insulin delivery has received the most attention in insulin formulations due to its high patient compliance and, more importantly, to its potential to mimic the physiologic insulin secretion seen in non-diabetic individuals. However, oral insulin delivery has two major limitations: the enzymatic barrier that leads to rapid insulin degradation, and the mucosal barrier that limits insulin’s bioavailability. Several approaches have been actively pursued to circumvent the enzyme barrier, with some of them receiving promising results. Yet, thus far there has been no major success in overcoming the mucosal barrier, which is the main cause in undercutting insulin’s oral bioavailability. In this review of our group’s research, an innovative silica-based, mucoadhesive oral insulin formulation with encapsulated-insulin/cell penetrating peptide (CPP) to overcome both enzyme and mucosal barriers is discussed, and the preliminary and convincing results to confirm the plausibility of this oral insulin delivery system are reviewed. In vitro studies demonstrated that the CPP-insulin conjugates could facilitate cellular uptake of insulin while keeping insulin’s biologic functions intact. It was also confirmed that low molecular weight protamine (LMWP) behaves like a CPP peptide, with a cell translocation potency equivalent to that of the widely studied TAT. The mucoadhesive properties of the produced silica-chitosan composites could be controlled by varying both the pH and composition; the composite consisting of chitosan (25 wt-%) and silica (75 wt-%) exhibited the greatest mucoadhesion at gastric pH. Furthermore, drug release from the composite network could also be regulated by altering the chitosan content. Overall, the universal applicability of those technologies could lead to development of a generic platform for oral delivery of many other bioactive compounds, especially for peptide or protein drugs which inevitably encounter the poor bioavailability issues.

关键词： insulin cell penetrating peptide mucoadhesive composites oral delivery

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Lingguizhugan Decoction, a Chinese herbal formula, improves insulin resistance in overweight/obese subjects

《医学前沿（英文）》 2022年第16卷第5期页码 745-759 doi: 10.1007/s11684-021-0880-3

摘要： Lingguizhugan Decoction (LGZG) has been investigated in basic studies, with satisfactory effects on insulin resistance in non-alcoholic fatty liver disease (NAFLD). This translational approach aimed to explore the effect and underlying mechanism of LGZG in clinical setting. A randomized, double-blinded, placebo-controlled trial was performed. A total of 243 eligible participants with NAFLD were equally allocated to receive LGZG (two groups: standard dose and low dose) or placebo for 12 weeks on the basis of lifestyle modifications. The primary efficacy variable was homeostasis model assessment of insulin resistance (HOMA-IR). Analyses were performed in two populations in accordance with body mass index (BMI; overweight/obese, BMI ≥ 24 kg/m²; lean, BMI < 24 kg/m ²). For overweight/obese participants, low-dose LGZG significantly decreased their HOMA-IR level compared with placebo (−0.19 (1.47) versus 0.08 (1.99),P = 0.038). For lean subjects, neither dose of LGZG showed a superior effect compared with placebo. Methylated DNA immunoprecipitation sequencing and real-time qPCR found that the DNA N6-methyladenine modification levels of protein phosphatase 1 regulatory subunit 3A (PPP1R3A) and autophagy related 3 (ATG3) significantly increased after LGZG intervention in overweight/obese population. Low-dose LGZG effectively improved insulin resistance in overweight/obese subjects with NAFLD. The underlying mechanism may be related to the regulation of DNA N6-methyladenine modification of PPP1R3A and ATG3. Lean subjects may not be a targeted population for LGZG.

关键词： insulin resistance non-alcoholic fatty liver disease Chinese herbal medicine randomized controlled trial DNA N6-methyladenine modification

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Identification of transporter proteins for PQQ-secretion pathways by transcriptomics and proteomics analysis

Hui Wan,Yu Xia,Jianghua Li,Zhen Kang,Jingwen Zhou

《化学科学与工程前沿（英文）》 2017年第11卷第1期页码 72-88 doi: 10.1007/s11705-016-1580-4

摘要： Pyrroloquinoline quinone (PQQ) plays a significant role as a redox cofactor in combination with dehydrogenases in bacteria. These dehydrogenases play key roles in the oxidation of important substrates for the biotechnology industry, such as vitamin C production. While biosynthesis of PQQ genes has been widely studied, PQQ-transport mechanisms remain unclear. Herein, we used both two-dimensional fluorescence-difference gel electrophoresis tandem mass spectrometry and RNA sequencing to investigate the effects of overexpression in an industrial strain of WSH-003. We have identified 73 differentially expressed proteins and 99 differentially expressed genes, a majority of which are related to oxidation-reduction and transport processes by gene ontology analysis. We also described several putative candidate effectors that responded to increased PQQ levels resulting from overexpression. Furthermore, quantitative PCR was used to verify five putative PQQ-transport genes among different PQQ producing strains, and the results showed that , and were upregulated in all conditions. Then the three genes were over-expressed in WSH-003 and PQQ production were detected. The results showed that extracellular PQQ of B932_1930 (a transporter) and B932_2186 (an ABC transporter permease) overexpression strains were enhanced by 1.77-fold and 1.67-fold, respectively. The results suggest that the proteins encoded by PqqB, B932_1930 and B932_2186 might enhance the PQQ secretion process.

关键词： 2D-DIGE pqqB pyrroloquinoline quinone RNA-Seq Vitamin C

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Parametric sensitivity analysis of cellular diaphragm wall

Xi CHEN, Wei XU

《结构与土木工程前沿（英文）》 2012年第6卷第4期页码 358-364 doi: 10.1007/s11709-012-0177-3

摘要： The deformation law of the cellular diaphragm wall in deep foundation pits was studied through numerical simulation. Based on the example of the dock wall in engineering, the full three-dimensional finite element model was used to simulate the excavation of the foundation pit. Interaction between the cellular diaphragm wall and the soil was also taken into account in the calculation. The results indicated that the maximum lateral displacement, which is the evaluation index of sensitivity analysis, appeared on the top of the interior longitudinal wall with an excavation depth of 10 m. The centrifuge model test was carried out to study the deformation regulation for a cellular diaphragm wall. The most sensitive factor was found by adjusting the length of the partition wall, the spacing of the partition wall and the thickness of the wall. In the end, a suggestion was proposed to optimize the cellular diaphragm by adjusting the length of the partition wall.

关键词： cellular diaphragm wall sensitivity analysis optimization centrifuge model test

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Influence of β-elemene on the secretion of angiotensin II and expression of AT1R in hepatic stellate

Ling YANG, Rui ZHU, Qingjing ZHU, Dan DAN, Jin YE, Keshu XU, Xiaohua HOU

《医学前沿（英文）》 2009年第3卷第1期页码 36-40 doi: 10.1007/s11684-009-0020-y

摘要： This study aims to investigate the influence of β-elemene on the secretion of angiotensin II (ANG II) and the expression of angiotensin receptor type 1 (AT1R) in hepatic stellate cells (HSCs). , HSC-T6 were cultured for 24 hours and then treated with different doses of β-elemene (2.5, 5 and 10 mg/L). A control group was also set up. The secretion of ANG II in the supernatant was detected by radioimmunoassay. The mRNA expression of AT1R at 4, 12 and 24 h after treatment was detected by reverse transcription-polymerase chain reaction (RT-PCR), respectively. The protein expression of AT1R was detected by western blot. At the 4th h, the ANG II secretion in the supernatant was significantly inhibited by 10 mg/L β-elemene compared with the control group ( <0.05), while 5.0 mg/L and 2.5 mg/L β-elemene had no inhibitory effect on the secretion of ANG II ( >0.05). At the time point of the 12th h, the secretion of ANG II in the supernatant treated with 10 mg/L and 5.0 mg/L β-elemene was significantly lower than the control ( <0.01, <0.05). Following the treatment with 5.0 mg/L and 2.5 mg/L β-elemene for 24 h, significant inhibition of ANG II secretion was observed ( <0.05), but 10 mg/L β-elemene had no such effect. β-elemene significantly reduced the amount of AT1R mRNA in HSCs after the treatment for 4, 12, and 24 h in a dose-dependent manner. The expression of AT1R protein also decreased after the treatment with β-elemene for 24 h. β-elemene can inhibit the secretion of ANG II and the gene and protein expression of AT1R, which may be the mechanism by which β-elemene prevents the progress of hepatic fibrosis.

关键词： liver cirrhosis beta-elemene hepatic stellate cells angiotensin II receptor angiotensin type 1

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Probability strength design of steam turbine blade and sensitivity analysis with respect to random parameters

DUAN Wei

《能源前沿（英文）》 2008年第2卷第1期页码 107-115 doi: 10.1007/s11708-008-0018-1

摘要： Many stochastic parameters have an effect on the reliability of a steam turbine blade during practical operation. To improve the reliability of blade design, it is necessary to take these stochastic parameters into account. An equal cross-section blade is investigated and a finite element model is built parametrically. Geometrical parameters, material parameters and load parameters of the blade are considered as input random variables while the maximum deflection and maximum equivalent stress are output random variables. Analysis file of the blade is compiled by deterministic finite element method and applied to be loop file to create sample points. A quadratic polynomial with cross terms is chosen to regress these samples by step-forward regression method and employed as a surrogate of numerical solver to drastically reduce the number of solvers call. Then, Monte Carlo method is used to obtain the statistical characteristics and cumulative distribution function of the maximum deflection and maximum equivalent stress of the blade. Probability sensitivity analysis, which combines the slope of the gradient and the width of the scatter range of the random input variables, is applied to evaluate how much the output parameters are influenced by the random input parameters. The scatter plots of structural responses with respect to the random input variables are illustrated to analyze how to change the input random variables to improve the reliability of the blade. The results show that combination of the finite element method, the response surface method and Monte Carlo method is an ideal way for the reliability analysis and probability strength design of the blade.

关键词： Probability sensitivity sensitivity analysis number cross-section statistical

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Effects of resistin on insulin signaling in endothelial cells

Zhizhen LI, Fangping LI, Jianhong YE, Li YAN, Zuzhi FU

《医学前沿（英文）》 2009年第3卷第2期页码 136-140 doi: 10.1007/s11684-009-0029-2

摘要： The objective of this study was to investigate the effects of resistin on insulin signaling in human umbilical vein endothelial cells (HUVECs). HUVECs were incubated with recombinant human resistin (0-100 ng/mL) for 24 h. Akt and endothelial nitric oxide synthase (eNOS) phosphorylation levels of endothelial cells under basal or insulin stimulated conditions were measured by Western blot. Nitric oxide (NO) production of HUVECs was also detected. The results showed that resistin could significantly inhibit Akt and eNOS phosphorylation and NO production in endothelial cells under insulin stimulated conditions ( < 0.05 control). But under basal conditions, treatment with resistin could result in a decrease in eNOS phosphorylation ( < 0.05 control) but had no effect on NO production and Akt phosphorylation levels. These findings suggested that resistin exerted an inhibitory effect on NO production by inhibiting insulin signaling and eNOS phosphorylation in endothelial cells.

关键词： resistin endothelium nitric oxide endothelial nitric oxide synthase Akt-binding protein mouse

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Wheel tracking methods to evaluate moisture sensitivity of hot-mix asphalt mixtures

Jie HAN,Harihar Shiwakoti

《结构与土木工程前沿（英文）》 2016年第10卷第1期页码 30-43 doi: 10.1007/s11709-016-0318-1

摘要： Existing test methods to determine moisture sensitivity in hot-mix asphalt (HMA) mixtures are time consuming and inconsistent. This research focused on wheel tracking devices to evaluate moisture sensitivity. The Asphalt Pavement Analyzer (APA) and the Hamburg Wheel Tracking Device (HWTD) were used for this research. Compacted cylindrical samples were fabricated using a Superpave Gyratory compactor. This study selected two most commonly used mixtures, SM-12.5A with PG 64-22 binder in overlay projects and SM-19A mixtures with PG 64-22 binder for major modification projects at Kansas Department of Transportation. Test results show that APA tests could induce stripping in most samples without any anti-stripping agent, which could be identified visually. However, APA results did not indicate any stripping inflection point while the HWTD results showed stripping inflection points, which are important to identify stripping potential of mixtures. The APA results show that wet tests are severe at lower temperatures. The HWTD results show improvement in the performance using anti-stripping agents at later stage. The HWTD test is more effective as a rapid test method in case of determining moisture sensitivity. Laboratory results from this study should be verified and correlated with field performance.

关键词： hot-mix asphalt moisture sensitivity rutting wheel tracking test

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标题作者时间类型操作

Decreasing complexity of glucose time series derived from continuous glucose monitoring is correlated with deteriorating glucose regulation

期刊论文

Inhibition of protein kinase B by Palmitate in the insulin signaling of HepG2 cells and the preventiveeffect of Arachidonic acid on insulin resistance

XIA Yanzhi, WAN Xuedong, DUAN Qiuhong, HE Shansu, WANG Ximing

期刊论文

Mechanism of insulin resistance in obesity: a role of ATP

期刊论文

Mechanisms of insulin resistance in obesity

null

期刊论文

Insulin resistance and the metabolism of branched-chain amino acids

null

期刊论文

Research on acoustic-structure sensitivity using FEM and BEM

ZHANG Jun, ZHAO Wenzhong, ZHANG Weiying