Naringin ameliorates H_(2)O_(2)-induced oxidative damage in cells and prolongs the lifespan of female Drosophila melanogaster via the insulin signaling pathway

Naringin exists in a wide range of Chinese herbal medicine and has proven to possess several pharmacological properties.In this study,PC12,HepG2 cells,and female Drosophila melanogaster were used to investigate the antioxidative and anti-aging effects of naringin and explore the underlying mechanisms.The results showed that naringin inhibited H_(2)O_(2)-induced decline in cell viability and decreased,the content of reactive oxygen species in cells.Meanwhile,naringin prolonged the lifespan of flies,enhanced the abilities of climbing and the resistance to stress,improved the activities of antioxidant enzymes,and decreased malondialdehyde content.Naringin also improved intestinal barrier dysfunction and reduced abnormal proliferation of intestinal stem cells.Moreover,naringin down-regulated the mRNA expressions of inr,chico,pi 3k,and akt-1,and up-regulated the mRNA expressions of dilp2,dilp3,dilp5,and foxo,thereby activating autophagy-related genes and increasing the number of lysosomes.Furthermore,the mutant stocks assays and computer molecular simulation results further indicated that naringin delayed aging by inhibiting the insulin signaling(IIS)pathway and activating the autophagy pathway,which was consistent with the result of network pharmacological predictions.

Simiao Wan alleviates obesity-associated insulin resistance via PKCε/IRS-1/PI3K/Akt signaling pathway based on network pharmacology analysis and experimental validation

Background:The purpose of the study was to investigatethe active ingredients and potential biochemicalmechanisms of Simiao Wan(SMW)in obesity-associated insulin resistance.Methods:An integrated network pharmacology method to screen the active compoundsand candidate targets,construct the protein-protein-interaction network,and ingredients-targets-pathways network was constructed for topological analysis to identify core targets and main ingredients.To find the possible signaling pathways,enrichment analysis was performed.Further,a model of insulin resistance in HL-7702 cells was established to verify the impact of SMW and the regulatory processes.Results:An overall of 63 active components and 151 candidate targets were obtained,in which flavonoids were the main ingredients.Enrichment analysis indicated that the PI3K-Akt signaling pathway was the potential pathway regulated by SMW in obesity-associated insulin resistance treatment.The result showed that SMW could significantly ameliorate insulin sensitivity,increase glucose synthesis and glucose utilization and reduce intracellular lipids accumulation in hepatocytes.Also,SMW inhibited diacylglycerols accumulation-induced PKCεactivity and decreased its translocation to the membrane.Conclusion:SMW ameliorated obesity-associated insulin resistance through PKCε/IRS-1/PI3K/Akt signaling axis in hepatocytes,providing a new strategy for metabolic disease treatment.

Prepartum body conditions affect insulin signaling pathways in postpartum adipose tissues in transition dairy cows

Background: Overconditioned dairy cows are susceptible to excessive lipolysis and increased insulin resistance during the transition period.The associations among body fat reserve,insulin resistance,and lipolysis in adipose tissues(AT) remain to be elucidated.Therefore,this study aimed to investigate whether excessive fat reserves influence the insulin signaling pathway in AT postpartum.Results: Twenty multiparous dairy cows were selected and assigned to one of two groups,according to prepartum body condition score(BCS): Control group(BCS = 3.0–3.5;n = 10) and Overconditioned group(BCS ≥ 4.0;n = 10).Blood samples were collected on days-14,-7,-4,-2,-1,0,1,2,4,7,and 14 relative to parturition.Subcutaneous AT were collected on day 2 following parturition for quantitative real-time polymerase chain reaction and western blot analyses.No differences were observed between the two groups in serum glucose,non-esterified fatty acids,β-hydroxybutyric acid,tumor necrosis factor(TNF)α,insulin,or leptin concentrations during the experimental period.Compared with the control cows,the overconditioned cows had lower serum triglyceride levels and higher adiponectin concentrations.In the AT postpartum,insulin receptor mRNA and protein levels were lower in the overconditioned cows than in the control cows,and no differences were found in glucose transporter 4 mRNA.Compared with the control cows,the overconditioned cows had lower mRNA levels of TNFα and higher mRNA levels of peroxisome proliferator-activated receptor gamma(PPARγ) in AT postpartum.The phosphorylated protein kinase B(AKT) content and phosphorylation rate of AKT were increased in the overconditioned cows compared with the control cows,which suggested that the downstream insulin signaling in AT was affected.Conclusions: In the present study,transition dairy cows with higher BCS did not show more fat mobilization.The changes of insulin signaling pathway in AT postpartum of overconditioned cows may be partly related to the expression of PPARγ and TNFα,and the secretion of adiponectin.

Pomegranate peel polyphenols alleviate insulin resistance through the promotion of insulin signaling pathway in skeletal muscle of metabolic syndrome rats

Insulin resistance(IR) has been considered to be an important causative factor of metabolic syndrome(Met S). The present study investigated whether pomegranate peel polyphenols(PPPs) could prevent the development of Met S by improving IR in rats. Male Sprague-Dawley(SD) rats were fed high fat diet(HFD) to induce Met S and supplemented with different dosages of PPPs for 12 weeks. The results showed that HFD-induced insulin resistant rats had disordered metabolism of blood glucose, blood lipid, and terrible muscle fiber morphology when compared with normal diet-fed rats, but PPPs treatment at a dosage of 300 mg/kg·day significantly reversed these negative effects. Moreover, in skeletal muscle tissue of insulin resistant rats, PPPs treatments significantly increased the protein expressions of insulin receptor(Ins R) and phosphorylated insulin receptor substrate 1(IRS-1), stimulated peroxisome proliferator activated receptor gamma(PPARγ) and phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT/PKB) signaling pathway, and aggrandized the protein levels of phosphorylated glycogen synthase kinase-3β(GSK-3β) and glucose transporter 4(GLUT4). Our results suggest that PPPs possess of the beneficial effects on alleviating IR by enhancing insulin sensitivity and regulating glucose metabolism.

Characterization of Wnt1-inducible Signaling Pathway Protein-1 in Obese Children and Adolescents

Wnt1-inducible signaling pathway protein-1(WISP1),a member of the CCN family,is increasingly being recognized as a potential target for obesity and type 2 diabetes mellitus.Recent studies have shown that WISP1 can regulate low-grade inflammation in obese mice,and circulating WISP1 levels are associated with obesity and type 2 diabetes mellitus in adults.Herein,we measured serum WISP1 levels in obese youth and explored its relationships with pro-inflammatory cytokine interleukin 18(IL-18)and other metabolic indexes.Totally,44 normal-weight and 44 obese children and adolescents were enrolled.Physical and laboratory data were recorded,and then serum levels of WISP1 and IL-18 were determined by enzyme-linked immunosorbent assays.Results showed that serum levels of WISP1 were significantly higher in obese children and adolescents than in normal-weight healthy controls (1735.444-15.29 vs. 1364.084-18.69 pg/mL).WISP1 levels were significantly positively correlated with body mass index (BMI)and BMI z-score (r=0.392,P=0.008;r=0.474,P=0.001,respectively) in obese group;circulating IL-18 was increased in obese individuals (1229.064-29.42 vs. 295.874-13.30 pg/mL).Circulating WISP1 levels were significantly correlated with IL-18 (r=0.542,P<0.001),adiponectin (r=0.585,P<0.001)and leptin (r=0.592,P<0.001).The multivariate stepwise regression analysis showed that higher IL-18 levels represented the main determinant of increased WISP1 levels after adjusting for BMI,waist circumference, fasting insulin,homeostatic model assessment of insulin resistance (HOMA-IR)and HbAlc in obese individuals (β=0.542,P=0.000).WISP1 can be involved in glucose/lipid metabolism in obese youth,which may be modulated by IL-18.Increased WISP1 levels may be a risk factor of obesity and insulin resistance,and WISP1 has a potential therapeutic effect on insulin resistance in obese children and adolescents.

UP780, a Chromone-Enriched <i>Aloe</i>Composition, Enhances Adipose Insulin Receptor Signaling and Decreases Liver Lipid Biosynthesis

Nutrigenomic studies were conducted to uncover the mechanism of action for the hypoglycemic and insulin sensitizing effects of UP780. From high fat diet-induced obesity mouse model for UP780, livers and white adipose tissues (WAT) from groups of lean control, high fat diet (HFD), and HFD treated with UP780 were collected for microarray study. Microarray generated gene expression changes were applied to Ingenuity Pathway Analysis for changes in canonical metabolic and signaling pathways. Microarray was validated by quantitative reverse transcriptase-polymerase chain reaction (QPCR), Western blots, liver triglyceride, liver cholesterol, liver steatosis, and insulin ELISA. UP780 treatment decreased liver gene expressions for multiple enzymes involved in fatty acid biosynthesis and triglyceride production. UP780 treatment increased gene expressions globally for the insulin receptor signaling pathway in WAT. Both liver triglyceride and liver cholesterol levels were significantly reduced by UP780 over HFD. The reduction of liver fat was confirmed by microscopic analysis of liver steatosis. Finally, UP780 significantly decreased fasting plasma insulin level over HFD. The mechanism of action for UP780 indicated a reduction of liver fat accumulation and an enhancement in adipose tissue insulin signaling pathway. This provided mechanistic explanation for the in vivo UP780 effects of enhanced insulin sensitiveity and decreased blood glucose in mouse diabetes and prediabetes models.

Circ_0053943 complexed with IGF2BP3 drives uveal melanoma progression via regulating N6-methyladenosine modification of Epidermal growth factor receptor

Numerous studies have characterized the critical role of circular RNAs(circRNAs)as regulatory factors in the progression of multiple cancers.However,the biological functions of circRNAs and their underlying molecular mechanisms in the progression of uveal melanoma(UM)remain enigmatic.In this study,we identified a novel circRNA,circ_0053943,through re-analysis of UM microarray data and quantitative RT-PCR.Circ_0053943 was found to be upregulated in UM and to promote the proliferation and metastatic ability of UM cells in both in vitro and in vivo settings.Mechanistically,circ_0053943 was observed to bind to the KH1 and KH2 domains of insulin-like growth factor 2 mRNA-binding protein 3(IGF2BP3),thereby enhancing the function of IGF2BP3 by stabilizing its target mRNA.RNA sequencing assays identified epidermal growth factor receptor(EGFR)as a target gene of circ_0053943 and IGF2BP3 at the transcriptional level.Rescue assays demonstrated that circ_0053943 exerts its biological function by stabilizing EGFR mRNA and regulating the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase(MAPK/ERK)signaling pathway.Collectively,circ_0053943 may promote UM progression by stabilizing EGFR mRNA and activating the MAPK/ERK signaling pathway through the formation of a circ_0053943/IGF2BP3/EGFR RNA-protein ternary complex,thus providing a potential biomarker and therapeutic target for UM.

基于IGF-1R/PI3K/AKT的益气固表丸对慢性阻塞性肺疾病模型大鼠的影响及作用机制研究

目的:益气固表丸对慢性阻塞性肺疾病(COPD)有明显的治疗作用,但具体作用机制尚不清楚。本研究旨在探讨益气固表丸对脂多糖(LPS)联合烟雾暴露构建慢性阻塞性肺病模型大鼠的治疗作用机制。方法:通过大鼠气管内灌注LPS和吸入香烟烟雾构建慢性阻塞性肺病模型,同时给予模型大鼠低、中、高剂量益气固表丸治疗14 d。观察呼吸参数及肺组织病理变化。采用酶联免疫吸附试验测定支气管肺泡灌洗液(BALF)及血清胰岛素样生长因子1型受体(IGF-1R)、白细胞介素-1β(IL-1β)、IL-10水平。采用蛋白质印迹法检测大鼠肺组织样品中胰岛素样生长因子1受体(IGF-1R)/PI3K/AKT信号通路组分的磷酸化状态。结果:与对照组和低剂量益气组比较,大剂量益气固表丸治疗可显著改善COPD大鼠呼吸参数,减轻肺损伤和炎症,降低BALF和血清炎症介质水平。此外,高剂量益气固表丸干预的COPD大鼠肺组织标本中磷酸化IGF-1R、p-PI3K、p-AKT、p-GSK3、p-mTOR蛋白水平显著降低。结论:益气固表丸对COPD有明显的治疗作用,可能与靶向IGF-1R/PI3K/AKT信号通路有关。

Loganin regulates glycolipid metabolism by influencing intestinal microbiota and AMPK signaling in obese mice

Objective: We aimed to observe the effects of loganin(Log) on serum glycolipid levels and probe the mechanisms focusing on intestinal flora and AMP-activated protein kinase(AMPK) signaling in obese mice.Methods: A high-fat diet was given for 12 consecutive weeks to generate the obesity model in institute of cancer research(ICR) mice. Body weight was measured weekly and fasting blood glucose(FBG) was determined every 2 weeks. Both the oral glucose tolerance test and the intraperitoneal insulin tolerance test were performed. The serum levels of total cholesterol(TC), triglyceride, high-density lipoproteincholesterol, low-density lipoprotein-cholesterol(LDL-C), and free fatty acids(FFA) were measured. The expression of key proteins in the AMPK signaling pathway in skeletal muscle tissue was detected by immunoblotting, and gut microbiota were characterized using 16S rDNA sequencing.Results: Log significantly decreased the body weight and the FBG in obese mice(P <.05), and it could restore FBG to normal levels. The total cholesterol, LDL-C, and FFA levels were significantly reduced by Log compared with the obese controls(TC: P =.0020;LDL-C: P =.0233;FFA: P =.0127), and the glucose tolerance of animals was significantly improved(P =.0477). The western blot results showed that Log could upregulate the protein expression of Adenosine 5‘-monophosphate(AMP)-activated protein kinase(AMPKa), Sirtuin 1(SIRT1), and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha(PGC1a) in skeletal muscle tissue of obese mice. 16S rDNA sequencing indicated that Log reduced the diversity of the gut flora in feces and altered the floral composition of obese mice.Conclusions: Log was effective in reducing body weight and improving glucolipid metabolism in obese mice, probably through activating AMPK signaling and regulating intestinal microbial diversity.

Correlation of MyD88 expression in the peripheral blood and placenta with the inflammatory response and insulin signal transduction in the placenta of patients with GDM

Objective: To study the correlation of MyD88 expression in peripheral blood and placenta with the inflammatory response and insulin signal transduction in the placenta of patients with gestational diabetes mellitus (GDM). Methods: The patients with GDM and healthy pregnant women who accepted antenatal care and gave birth in Guangyuan First People's Hospital between March 2015 and June 2017 were selected as the research subjects and enrolled in the GDM group and control group for the study respectively;the peripheral blood was collected before delivery to determine the MyD88 mRNA expression, and the placental tissue was collected after delivery to determine the mRNA expression of MyD88, inflammatory response molecules and insulin signal transduction molecules. Results: MyD88 mRNA expression levels in the peripheral blood and placenta of GDM group were significantly higher than those of control group, and the MyD88 mRNA expression in the peripheral blood was positively correlated with the MyD88 mRNA expression in the placenta;IL-1β, IL-6, RBP4, Chemerin, Resistin and PTP1B mRNA expression levels in the placenta of GDM group were significantly higher than those of control group whereas IRS1, ISR2, p-PI3K and GLUT4 protein expression levels were significantly lower than those of control group;IL-1β, IL-6, RBP4, Chemerin, Resistin and PTP1B mRNA expression levels in the placenta of GDM group of patients with high MyD88 expression were significantly higher than those of patients with low MyD88 expression whereas IRS1, ISR2, p-PI3K and GLUT4 protein expression levels were significantly lower than those of patients with low MyD88 expression. Conclusion:The expression of MyD88 in peripheral blood and placenta increase in patients with GDM and the change of MyD88 expression in peripheral blood could reflect the abnormality of inflammatory response and insulin signal transduction in the placenta.

Functional evaluation of the insulin/insulin-like growth factor signaling pathway in determination of wing polyphenism in pea aphid

Wing polyphenism is a common phenomenon that plays key roles in environmental adaptation of insects.Insulin/insulin-like growth factor signaling(IIS)pathway is a highly conserved pathway in regulation of metabolism,development,and growth in metazoans.It has been reported that IS is required for switching of wing morph in brown planthopper via regulating the development of the wing pad.However,it remains elusive whether and how IIS pathway regulates transgenerational wing dimorphism in aphid.In this study,we found that pairing and solitary treatments can induce pea aphids to produce high and low percentage winged offspring,respectively.The expression level of ILP5(insulin-like peptide 5)in maternal head was significantly higher upon solitary treatment in comparison with pairing,while silencing of ILP5 caused no obvious change in the winged offspring ratio.RNA interference-mediated knockdown of FoxO(Forkhead transcription factor subgroup O)in stage 20 embryos significantly increased the winged offspring ratio.The results of pharmacological and quantitative polymerase chain reaction experiments showed that the embryonic insulin receptors may not be involved in wing polyphenism.Additionally,ILP4 and ILP11 exhibited higher expression levels in 1st wingless offspring than in winged offspring.We demonstrate that FoxO negatively regulates the wing morph development in embryos.ILPs may regulate aphid wing polyphenism in a developmental stage-specific manner.However,the regulation may be not mediated by the canonical IIS pathway.The findings advance our understanding of IIS pathway in insect transgenerational wing polyphenism.

IGF-I对视网膜新生血管形成的调控及其信号转导机制

视网膜新生血管形成是多种眼病的共同病理过程。IGF-1及其相关因子和信号转导机制对视网膜新生血管的形成和发展起重要的调控作用。IGF-I是一种结构和功能都与胰岛素类似的多肽类神经营养因子,具有广泛的生物学活性,与其受体结合后,能激活酪氨酸蛋白激酶,磷酸化特异性底物,激活PI-3K/Akt和MAP-K依赖信号途径后导致HIF-1α、JNK/AP-1激活和VEGFmRNA表达,调控细胞的生长、增生、分化、迁移、抑制细胞凋亡,通过对IGF-I的干预,可能是预防视网膜新生血管的一个新途径。

二苯乙烯苷调控胰岛素/IGF-1信号通路延缓大鼠睾丸间质细胞衰老的作用机制

采用自由基损伤的方法建立大鼠睾丸间质细胞衰老模型,用流式细胞术检测各组细胞周期的变化;应用RT-qPCR、免疫荧光和Western blot技术检测睾丸间质细胞胰岛素/IGF-1信号传导通路关键基因的表达水平.结果显示:与正常组相比,衰老组β-半乳糖苷酶阳性细胞率可达60%以上(P<0.05),G1期所占比重明显增加,S期所占比重明显减少(P<0.05).胰岛素/IGF-1信号传导通路关键基因表达变化:IRS1、IGF-1、IRS2、INSR在衰老组的表达水平明显低于正常组(P<0.05),IGFBP3在衰老组的mRNA表达水平明显高于正常组(P<0.05),二苯乙烯苷可逆转上述现象,上调IGF-1、INSR、IRS1、IRS2表达,下调IGFBP3的mRNA表达.结果表明二苯乙烯苷通过调控胰岛素/IGF-1信号传导通路延缓睾丸间质细胞衰老.

绿原酸对昆虫病原线虫卡森斯氏线虫寿命及抗氧化活性的调控

为观察绿原酸(CGA)对昆虫病原线虫寿命及抗氧化活性的影响,探究绿原酸对线虫生命活动的调控机制,本文以卡森斯氏线虫作为抗衰老模型,用不同浓度的绿原酸(0、50、100、500、1000μmol/L)处理,探究其对卡森斯氏线虫寿命、抗氧化活性、脂褐素水平、相关基因m RNA表达水平的调控作用,初步探讨绿原酸的潜在作用机理。结果表明,与空白对照组相比,用100μmol/L绿原酸刺激线虫后使处理组最长寿命增加了36.36%,显著抑制体内脂褐素的积累;且该浓度刺激线虫体内的SOD和CAT酶活力,分别提高了1.97倍和2.47倍;此外,q RT-PCR结果显示,100μmol/L CGA喂养线虫后,daf-16、gst-4基因转录水平相比对照分别提高了1.78、3.51,而daf-2基因转录水平呈下降的趋势,降低了0.13。综上可知,绿原酸通过胰岛素/IGF-1信号通路提高昆虫病原线虫卡森斯氏线虫机体的抗氧化能力并延长昆虫病原线虫的寿命。

Genes required for the functions of olfactory AWA neuron regulate the longevity of Caenorhabditis elegans in an insulin/IGF signaling-dependent fashion

Objective To investigate the interaction between the genes required for the functions of AWA olfactory neuron and insulin/IGF signaling in regulating the longevity of nematode Caenorhabditis elegans （C. elegans）. Methods The mutants that had loss-of-function mutation of the genes required for AWA, AWC, ASE, and AFD sensory neurons were employed. Lifespan, the speed of pharynx pumping, the intestinal autofluorescence, the dauer formation, and the brood size were examined. Rescue experiments were performed to confrm the role of the genes required for the functions of AWA neuron in regulating lifespan. Moreover, genetic interactions between genes required for the functions of AWA neuron and insulin/ IGF signaling were investigated. Results Mutations of odr-7, odr-2, and odr-3 genes required for the functions of AWA neuron significantly increased the mean lifespan of nematodes and slowed the accumulation of intestinal autofluorescence. Besides, these mutations were closely associated with higher pumping rates during aging. However, mutation of odr-7, odr- 2, or odr-3 did not obviously affect the brood size or the dauer formation, and the regulation of longevity by odr-7, odr-2, and odr-3 was temperature-independent. In contrast, mutations of genes required for the functions of ASE, AWC, and AFD sensory neurons did not infuence the nematode lifespan. Moreover, expression of odr-7, odr-2 and odr-3 in AWA neuron could completely or largely restore the altered lifespan in odr-7, odr-2 and odr-3 mutants. Furthermore, genetic interaction assay demonstrated that the extended lifespan in odr-7 mutant could be suppressed by daf-16 mutation and enhanced by daf- 2 or age-1 mutation, whereas mev-1 and pha-4 were not required for the long lifespan of odr-7 mutant. Conclusion The genes required for the function of AWA sensory neuron could regulate the nematode longevity in an insulin/IGF signaling-dependent fashion in C. elegans.

阿魏酸通过胰岛素/IGF信号通路和DAF-16促进秀丽隐杆线虫寿命和应激抵抗力

【目的】观察阿魏酸对秀丽隐杆线虫寿命及应激抵抗能力的影响,探究其可能机制。【方法】使用秀丽隐杆线虫作为抗衰老模型,给予不同浓度的阿魏酸(0、1、10、50 mmol/L),探究其对线虫寿命、抗应激能力、脂褐素水平的调控作用;使用qPCR筛选衰老相关基因,采用daf-2(DR1572)、daf-16(CF1038)突变体线虫,对阿魏酸的潜在作用机理进行初步探讨。【结果】与空白对照组相比,阿魏酸能明显延长秀丽隐杆线虫寿命并提高抗氧化应激和热应激能力(P<0.001),抑制与衰老相关的脂褐素的沉积(P<0.001),同时不影响生育力和发育(P>0.05)。用50 mmol/L阿魏酸组喂养线虫后,daf-2、akt-2和age-1基因的mRNA表达水平下调(P<0.05),daf-16基因的mRNA表达水平上调(P<0.05),并上调其下游靶基因sod-3、clk-2的mRNA表达,以及下调ctl-1、dod-17的mRNA表达(P<0.05)。50 mmol/L阿魏酸处理后DAF-16::GFP在细胞核定位的线虫比例从(5.3±1.5)%增加到(28±3)%。daf-2(DR1572)、daf-16(CF1038)突变体线虫在50 mmol/L阿魏酸处理后,寿命未见明显延长(P>0.05)。【结论】阿魏酸可通过胰岛素/IGF信号通路,促进DAF-16的核定位,提高机体应激抵抗能力,并延长线虫寿命。

隔药饼灸对高脂血症兔IGF-1/Sp1蛋白及基因表达的影响

目的探究隔药饼灸对高脂血症兔胰岛素样生长因子1(insulin-like growth factor 1,IGF-1)/特异性蛋白1(specificity protein 1,Sp1)蛋白及基因表达的影响。方法将36只雄性新西兰兔随机分为正常组、模型组和隔药饼灸组,每组12只。造模各组予高胆固醇配方饲料喂养8周制备高脂血症模型,正常组普食饲养。模型组捆绑操作,隔药饼灸组隔药饼灸干预,施灸穴位分为腹背两组,腹组为“巨阙”与双侧“天枢”“丰隆”,背组为双侧“心俞”“肝俞”“脾俞”,每天只施灸一组穴位,两组穴位交替施灸,持续8周。干预8周后,取各组兔血清、主动脉组织及肝组织样本,采用ELISA、RT-PCR技术检测IGF-1、Sp1指标。结果(1)干预8周后,与正常组比较,模型组血清IGF-1、Sp1含量上升(P<0.01);与模型组比较,隔药饼灸组血清IGF-1、Sp1含量下降(P<0.01)。(2)与正常组比较,模型组主动脉IGF-1的mRNA表达量显著上升(P<0.001),与模型组比较,隔药饼灸组主动脉IGF-1的mRNA表达量下降(P<0.01)。(3)与正常组比较,模型组肝组织IGF-1和Sp1的mRNA表达量显著上升(P<0.001,P<0.01);与模型组比较,隔药饼灸组肝组织IGF-1和Sp1的mRNA表达量下降(P<0.01)。结论隔药饼灸可能影响IGF-1/Sp1信号通路,通过胆固醇逆转运环节,调节LDL-C的摄取和转运而缓解高脂血症。

Protective effects of Huanglian Wendan Decoction aganist cognitive deficits and neuronal damages in rats with diabetic encephalopathy by inhibiting the release of inflammatory cytokines and repairing insulin signaling pathway in hippocampus

Huanglian Wendan decoction(HLWDD) has been used for the treatment of symptom of "Re", one of major causes in diabetes and metabolic disorders, according to the theory of traditional Chinese medicine. The present study aimed at investigating the cerebral protective effects of HLWDD on diabetic encephalopathy(DE), one of the major diabetic complications. The effects of HLWDD and metformin were analyzed in the streptozocin(STZ) + high-glucose-fat(HGF) diet-induced DE rats by gastric intubation. In the present study, the effects of HLWDD on cognition deficits were investigated after 30-day intervention at two daily dose levels(3 and 6 g·kg^(-1)). To explore the potential mechanisms underlying the effects of HLWDD, we detected the alterations of neuronal damages, inflammatory cytokines, and impaired insulin signaling pathway in hippocampus of the DE rats. Based on our results from the present study, we concluded that the protective effects of HLWDD against the cognitive deficits and neuronal damages through inhibiting the release of inflammatory cytokines and repairing insulin signaling pathway in hippocampus of the DE rats.

Chromium-containing traditional Chinese medicine, Tianmai Xiaoke Tablet improves blood glucose through activating insulin-signaling pathway and inhibiting PTP1B and PCK2 in diabetic rats

OBJECTIVE： Chromium is an essential mineral that is thought to be necessary for normal glucose homeostasis. Numerous studies give evidence that chromium picolinate can modulate blood glucose and insulin resistance. The main ingredient of-13anmai Xiaoke （TMXK） Tablet is chromium picolinate. In China, TMXK Tablet is used to treat type 2 diabetes. This study investigated the effect of TMXK on glucose metabolism in diabetic rats to explore possible underlying molecular mechanisms for its action. METHODS： Diabetes was induced in rats by feeding a high-fat diet and subcutaneously injection with a single dose of streptozotocin （50 mg/kg, tail vein）. One week after streptozotocin-injection, model rats were divided into diabetic group, low dose of TMXK group and high dose of TMXK group. Eight normal rats were used as normal control. After 8 weeks of treatment, skeletal muscle was obtained and was analyzed using Roche NimbleGen mRNA array and quantitative polymerase chain reaction （qPCR）. Fasting blood glucose, oral glucose tolerance test and homeostasis model assessment of insulin resistance （HOMA-IR） index were also measured. RESULTS： The authors found that the administration of TMXK Tablet can reduce the fasting blood glucose and fasting insulin level and HOMA-IR index. The authors also found that 2 223 genes from skeletal muscle of the high-dose TMXK group had significant changes in expression （1 752 increased, 471 decreased）. Based on Kyoto encyclopedia of genes and genomes pathway analysis, the most three significant pathways were ＂insulin signaling pathway＂, ＂glycolysis/ gluconeogenesis＂ and ＂citrate cycle （-ICA）＂. qPCR showed that relative levels of forkhead box 03 （Fox03）, phosphoenolpyruvate carboxykinase 2 （Pck2）, and protein tyrosine phosphatase 1B （Ptplb） were significantly decreased in the high-dose TMXK group, while v-akt murine thymoma viral oncogene homolog 1 （Aktl） and insulin receptor substrate 2 （Its2） were increased. CONCLUSION： Our data show that TMXK Tablet reduces fasting glucose level and improves insulin resistance in diabetic rats. The mechanism may be linked to the inactivation of PTP1B and PCK enzymes, or through intracellular pathways, such as the insulin signaling pathway.

Micro RNA-185 regulates expression of lipid metabolism genes and improves insulin sensitivity in mice with non-alcoholic fatty liver disease

AIM: To assess the regulatory effect of microRNA-185 (miR-185) on lipid metabolism and the insulin signalling pathway in human HepG2 hepatocytes and a high-fat diet mouse model.